Sepsis Flashcards
ABCCs of Sepsis
Is a framework to assist in understanding the pathophysiology of sepsis. A stands for
Arachidonic Acid, B for Bradykinin, C for Complement and C for Coagulation.
Arachidonic Acid
A highly reactive substance that contributes to:
organ dysfunction,
vascular permeability,
and prolongs inflammation.
The vascular permeability leads to third spacing of fluid and decreases in preload.
Bradykinin
Stimulates mast cells and release of histamine as
well as Arachidonic Acid.
This leads to vasodilatation and permeability.
Coagulation
In sepsis, the coagulation cascades become overstimulated resulting in the formation of micro-clotting in the vascular bed resulting in poor end organ perfusion.
Complement
proteins that stimulate phagocytosis, promote
immune and inflammatory responses
The release of complement proteins causes mast cells to be stimulated resulting in vasodilatation and promotion of the coagulation cascade.
Continuum of sepsis
SIRS Sepsis severe sepsis septic shock MODS death
Early Goal Directed Therapy
increase supply of oxygen to the body, first through improvement of preload,
if fluid not effective vasoactive drugs such as levophed, blood products to increase carrying capacity and demand management via sedation, analgesics or NMB.
Parameters monitored for treatment effectiveness include MAP, ScV02 and Lactate.
Sepsis
Sepsis is a systemic inflammatory response to an infection.
Results in :
vasodilation,
third spacing of fluid.
Septic shock
This is a type of shock related sepsis. Patient experiences low perfusion, despite efforts at
fluid resuscitation and use of vasoactive drugs.
Shock
Shock is an acute and widespread process that results in massive organ dysfunction as the
result of poor perfusion. Causes are numerous but include hypovolemia, cardiogenic,
neurogenic, anaphylactic and sepsis
SIRS
Systemic Immune Response Syndrome is a whole body response to any insult. The insult
could be burns, infection or trauma. The immune system becomes hyperactive resulting in
vasodilation, increased vascular permeability and inappropriate clotting.
Vasopressin IV
A naturally occurring substance in the body also known as anti-diuretic hormone (ADH). It is
part of the RAAS compensatory mechanism. It is used in sepsis to support vascular tone and works synergistically with levophed to improve EOP.
Briefly describe the patho of sepsis
Bacteria in the blood causes release of endotoxins (gram neg) and exotoxins (gram pos) causing pro-inflammatory cytokines
Cytokines activate the (ABCC) complement and coagulation system, kinin system and arachadonic
causing vasodilation and vascular leaking
MECHANICAL VENTILATION-PROTECTIVE LUNG STRATEGIES RECOMMENDED
LOWER TIDAL VOLUMES (6CC/KG)
• HIGHER PEEP (AS NEEDED TO SUPPORT GAS EXCHANGE)
• LIMITING PLATEAU PRESSURE TO 30 CMH2O
• USE OF NEUROMUSCULAR BLOCKADE DRUGS TO FACILITATE MV, LIMITED TO <48 HOURS
Sepsis definition
a life threatening condition that arises when the body’s response to infection injures its own tissues and organs
Systemic inflammatory response + suspected or confirmed infection
sepsis continuum
Infection->sepsis->septic shock->multiple organ dysfunction syndrome->death
SIRS
Temperature >38C or <36C Heart Rate > 90bpm Resp. Rate >20/min. or PaCO2 <32 mmHg WBC >12 or <4 or 10% band (immature cells)
Septic shock
hypotension despite adequate fluid resuscitation and Need for vasopressors
Septic shock criteria
- Diagnosed with Sepsis
- Require vasopressor therapy to
maintain MAP >65 - Lactate > 2mmol/L despite
adequate fluid resuscitation
Risk for sepsis
• Age: <1 year, >65 years • Immunocompromising conditions and/or medications • Multiple comorbidities • Chronic diseases • Obstructions (e.g. calcuous cholecystitis) • Hospital acquired infection (e.g. VAP) • Breaks in skin (trauma, invasive medical devices, wounds) • Incomplete antibiotic regimes • Surgery and diagnostic procedures • Antibiotic resistant organisms
VIPP
Overall goal is to keep injury/infection LOCALIZED and under CONTROL
VASCULAR RESPONSE
IMMUNE RESPONSE
PLATELETS
PLASMA PROTEIN RESPONSE
VASCULAR RESPONSE to infection
Vasodilation Capillary Permeability HISTAMINE BRADYKININ PROSTAGLANDINS
IMMUNE RESPONSE to infection
Neutrophils
Monocytes /Macrophages
Antibody
Antigen
PLATELETS response to infection
Coagulation
Fibrinolysis
PLASMA PROTEIN RESPONSE to infection
Compliment cascade
ABCCs of sepsis
Arachidonic
Bradykinin
Coagulation
Complement
Arachidonic
Prostoglandins:
Vasodilation
Increase permeability
Tromboxane:
Promotes platelet aggregation
-Increased permeability: fluid shifting from the vascular space to the interstitial space
-Decreased preload
-Decreased ventilation and gas exchange
if the fluid shifts in the lungs
Bradykinin
Mast Cell Degranulation
Histamine Release = Potent vasodilation
- Vasodilator
- Increased capillary permeability
- Mast-cell->histamine->vasodilation
- Mast cell->AA pathway->Further vasodilation and capillary permeability
- Decreased preload
- Decreased afterload
Coagulation
Fibrin formation/Broken plasminogen pathway
Microemboli formation
- Coagulation cascade becomes systemic
- Anticoagulation pathway fails->Microemboli throughout the systemic circulation->blood flow impeded->decrease cellular oxygen supply->end organ dysfunction
- AA pathway further triggered
- Kinin cascade triggered
- Complement pathway triggered
Complement
MAC Intensify inflammation Damage endothelium Cell Adhesion Cell Death/Lysis
Stimulation of phagocytosis
- Promotion of immune response
- Promotion of inflammatory response (increased permeability and vasodilation)
- Stimulation of mast cells->histamine release ->vasodilation
Primary outcomes of the dysregulated inflammatory response in sepsis (SIRS):
Systemic vasodilation (hypotension) Increased capillary permeability Inappropriate clotting in the microvasculature (through activation of coagulation system and failure of the fibrinolytic system) Maldistribution of blood flow Diminished myocardial contractility Poor end-organ perfusion Degreased cellular oxygenation Organ dysfunction
Medications which act on Arachidonic Acid pathway
- Steroids (Phospolipase release inhibition)
- NSAIDs (Non selective COX inhibitor)
- Celebrex (COX 2 Inhibitor)
- ASA (thromboxane inhibition)
- Asthma drugs (Leukotrienese inhibition)
Where do the ABCC’s effect patients O2 Supply and Demand?
Vasodilation decreased afterload
Cap permeability decreases preload
qSOFA
GCS <15
RR >22 bpm
SBP < 100mmHg
1 HOUR BUNDLE
- Measure Lactate
- Obtain blood cultures prior to administration of antibiotics
- Administer broad spectrum antibiotics
- Administer 30ml/kg crystalloid for hypotension or
lactate > 4mmol/L - Apply vasopressors if patient is hypotensive during or
after fluid resuscitation to maintain MAP >65mmHg
INTERVENTIONS IN THE FIRST 6 HOURS
- ATTAINING A MAP > 65MMHG
- NORMALIZING LACTATE
- ADEQUATE FLUID RESUSCITATION
- PRELOAD ASSESSMENT
- VASOPRESSOR THERAPY
FLUID RESUSCITATION
CRYSTALLOID AND COLLOID IV FLUID THERAPY A BALANCE BETWEEN THE TWO
- BEGIN WITH 30M/KG RECOMMENDATION, THEN ONGOING ASSESSMENT OF PRELOAD
- 2L WITHIN FIRST HOUR
- 2 WITHIN THE FIRST 6-8 HOURS
FLUID RESPONSIVENESS
• INCREASE IN STROKE VOLUME
• INCREASE IN CARDIAC OUTPUT
• ‘PRELOAD RESERVE’ OR ‘ROOM FOR MORE PRELOAD’
• INCREASE IN MAP, DECREASE IN HR, CHANGE IN PULSE CONTOUR
• NOTICEABLE RESPONSE TO SMALL VOLUMES OF FLUID-ASCENDING PART OF THE STARLING
CURE
• NO RESPONSE-ON THE FLAT PART OF THE CURVE
PASSIVE LEG RAISE
- RAISING THE PATIENT’S LEG WHILE IN SUPINE
- FACILITATES VENOUS RETURN
- IMMEDIATE IMPROVEMENT IN PRESSURES->ROOM FOR MORE PRELOAD
FLUID CHALLENGE
- RAPID ADMINISTRATION OF 250-500 CC IV FLUID (NS)
* IMPROVEMENTS IN HEMODYNAMICS->ROOM FOR MORE PRELOAD
When do we use VASOACTIVE DRUGS
- NOT RESPONDING TO FLUID RESUSCITATION
* MAP <65MMHG IN THE PRESENCE OF ADEQUATE PRELOAD
VASOACTIVE DRUGS of choice for sepsis
• LEVOPHED (NOREPINEPHRINE)
• VASOPRESSIN (0.03UNITS/MIN) WHEN NOT RESPONDING TO LEVO TO ATTAIN MAP GREATER
THAN OR EQUAL TO 65
• PERSISTENT HYPOPERFUSION DESPITE FLUIDS AND PRESSORS->DOBUTAMINE
