Sepsis Flashcards
(41 cards)
Define SIRS
2 of: 3 Ts with White sugar
Tachycardia 90+
Tachypnoea 20+ (or PaCO2 below 32)
Temperature under 36 or above 38
WBCs below 4 or above 12
Define sepsis
SIRS with a known or suspected infection source
Define severe sepsis
Sepsis with evidence of end-organ dysfunction
e.g.
hypotension (below 90 or more than 40 below baseline)
low urine output below 0.5ml/kg/hour
lactate above 4
Define septic shock
Sepsis refractory to fluid resuscitation e.g. persistent BP below 90
Describe the process of sepsis (without going into detail of ARDS or DIC)
Gram +ve LPS or gram -ve endotoxin (PAMPs) are recognised by TLR 2 and TLR 4 (PRRs) respectively, of neutrophils and monocytes (remember, this is in blood).
That causes activation of the neutrophils and monocytes which causes IL-1 and TNF-alpha release, which causes further inflammatory cell recruitment (e.g. mast cells releasing histamine, other WBCs releasing cytokines etc).
The activated WBCs release a variety of cytokines including IL-6, IL-8, PAF, as well as NO and reactive oxygen species. These cause activation of endothelial cells (endothelial activation). Note also anti-inflammatory cytokines such as IL-10 are released too.
Endothelial activation causes increased vascular permeability and vasodilation (also due to NO), which decreases blood pressure and subsequently contributes to organ hypoperfusion.
The reactive oxygen species cause microdamage to vessels which causes tissue factor release which leads to microthrombosis formation which decreases perfusion further. The microthromboses cause flow stasis in small vessels which decreases clearance of pro-coagulatory and pro-inflammatory factors, and so microthrombosis increases even more. PAF circulating also causes platelets to stick to the clots. Note that in all of this time PLTs are dropping, and so are anti-coagulating factors, which contributes to risk of haemorrhage - the combination of thromboses and haemorrhage are DIC (more detail later). The activated endothelial cells also decrease release of PAI which is usually anti-coagulant, so its reduction contributes further to coagulation.
The bacterial PAMPs also activate complement which causes further release of cytokines through anaphylotoxin production, and further inflammation through MAC complex formation and opsonin formation.
The whole process leads to vasodilation, increased vascular permeability and microvascular thrombosis which decreases tissue perfusion and leads to hypotension and multi-organ failure.
Describe DIC
DIC is an abnormal imbalance of the pro-coagulation and anti-coagulation mechanisms in the body leading to pro-thrombotic and pro-haemorrhagic states coexisting, leading to formation of micro and macrothrombi formation along with haemorrhage.
The bacterial toxins cause WBC activation causing a cytokine storm, and one of the goodies released are reactive oxygen species which cause damage to vessels. Vessel damage causes TF release. Also, endothelial activation by the cytokines (e.g. IL-6, IL-8) causes TF release and decreased production of PAI. This leads to formation of microthrombi by the following process:
Factor VII is converted to VIIa due to trauma.
TF which has been released combines with VIIa to form factor tenase.
Factor tenase (TF/VIIa) converts factor X to factor Xa.
Factor Xa converts prothrombin to thrombin.
Thrombin converts fibrinogen to fibrin.
Fibrin and factor XIIIa form cross-linked fibrin clots.
So clots are formed due to increased TF (TF is always available in tiny amounts in the circulation).
Also though, anti-coagulation factors such as antithrombin are being used up due to increased fibrin formation, and so this provides a positive feedback loop.
On top of that, plasminogen is converted to plasmin due to thrombin presence, and plasmin converts fibrin to FDPs, which are anticoagulatory and so this increases haemorrhage risk. Also, plasmin activates kinin and complement pathways ultimately leading to vasodilation and increased vascular permeability.
In all of this, platelet forming products diminish significantly, meaning diffuse haemorrhage occurs.
DIC is the combination of diffuse micro- and macrothrombus formation due to procoagulatory state, along with diffuse haemorrhage due to the using up of platelet forming products.
Describe ARDS
The lungs are the first port of call for blood returning from the body to the heart, and this blood will be full of cytokines in an inflammatory state.
When cytokines including IL-1 and TNF-alpha arrive at respiratory capillaries, the capillary endothelial cells are activated and vasodilate and permeability increases.
Neutrophils and monocytes are activated by the cytokines and marginalise and diapedese into the interstitial fluid through the activated endothelia (which express adhesins), and then enter the alveoli.
Within the alveoli, activated neutrophils and macrophages release leukotrienes, proteases, PAFs and other cytokines, causing a number of effects:
- Fluid entry (edema)
- Hyaline membrane formation
- Epithelial necrosis
- Surfactant inactivation
- TGF beta and PGF release causing fibroblast and collagen synthesis (healing).
This all greatly disrupts gas exchange leading to sudden or rapid onset hypoxaemia, cyanosis, increased respiratory rate, respiratory acidosis etc.
If sepsis is identified, what do you do?
ABCDE or:
O2: high flow; maintain above 94%
FLUIDS: 20ml/kg fluid challenge, 500mL boluses*
LACTATE
URINE OUTPUT (catheter)
INFECTION SCREEN: fbc, crp, blood cultures x 2, swabs, sputum/urine gram stain, mc+s, dip
DRUGS: IV ABx
- Stop fluids when:
- MAP above 65
- sBP satisfactory
- No further augmentation
- CVP 8-12
- Pulmonary oedema signs
A: maintain airway B: high flow oxygen C: IV access, bloods, IV fluids D: glucose, GCS/AVPU, pupils E: rashes etc
What can you do if you’re giving fluids to resuscitate and it’s not working or they develop pulmonary oedema / ARDS?
Vasopressors:
- Norepinephrine if CO high
- Epinephrine if CO low
- Phenylephrine if tachycardia / arrythmia
Inotropes:
- Dobutamine
What is early goal directed therapy?
- MAP above 65
- CVP 8-12
- U/O above 0.5ml/kg/hour
What other precautions are important for sepsis?
VTE prophylaxis
Insulin to maintain glucose
E Coli
UTI, biliary tract
S. aureus
Skin, vascular
N. meningitidis
CNS
S. pneumoniae
Resp
Pseudomonas
UTI,
resp, immunocomprimised
Strep pyogenes
Skin, soft tissue
Strep A
Skin, soft tissue
Gram +ve cocci
Skin
Listeria
Bowel, food
Extremes of age
Immunocomprimised
Clostridium
Bowel
Gas gangrene
Food
Bacteroides
Bowel, pelvis
Klebsiella
Abdo
Proteus
UTI
HPB
