Lecture 28 Sepsis and septic shock Flashcards
What are components of pathophysiology of sepsis?
Over-Inflammation: host cells bind toll-like receptors ⇒ increased release of TNFs, ILs ⇒ activate neutrophils
Profound Hypotension: neutrophils injure endothelium ⇒ release of mediators which increase vascular permeability ⇒ loss of fluid (this and edema) ⇒ release of NO = vasodilation
Hypoperfusion and Tissue Damage: endothelium produces tissue factors = activation of clotting cascade ⇒ leads to microvascular thrombi lodging in vessels
Organ Damage: vasodilation and increased vascular permeability and fluid loss = hypotension ⇒ this + intravascular coagulation ⇒ hypoperfusion and damage to vital organs (kidneys, brain, heart, liver, lungs)
Reduced Cardiac Output: hypotension and fluid loss ⇒ reduced preload, heart tissue damage = reduced CO
IN SUMMARY: hypotension + reduced CO + microthrombi = profound hypotension + reduced tissue perfusion + end organ damage
What is systemic inflammatory response syndrome (SIRS)?
old term for systemic response to a wide range of stresses
criteria include TWO or more of: temp >38 or <36, HR > 90, RR > 20 or PaCO2 <32, WBC >12 (or <4) x 10^9/L or >10% immature (band) forms
What is sepsis?
the systemic response to infection,, old definition is SIRS + proven or clinically suspected infection
life-threatening organ dysfxn caused by dysregulated host response to infection
organ dysfxn - acute change in total Sequential Organ Failure Assessment (SOFA) score >/= 2 points
What is the quick SOFA (qSOFA) Criteria?
may be used at bedside to identify pt likely to have prolonged ICU stay or die in hospital
at least 2 of: RR >/= 22, altered mentation, SBP </= 100
What is severe sepsis?
old definition,, sepsis associated with dysfxn of organ(s) distant from the site of infection, hypoperfusion, or hypotension
may include: lactic acidosis, oliguria, acutely altered mental status, acute lung injury
What is septic shock?
sepsis with hypotension that doesn’t respond to adequate fluid resuscitation and requires vasopressor tx
sepsis with circulatory, cellular, and metabolic dysfxn associated with higher risk of mortality than sepsis alone
pt require vasopressors to maintain MAP >/= 65 and have serum lactate > 2 mmol/L (in absence of hypovolemia)
What are the most common sources of sepsis?
pneumonia (most common), intra-abdominal infections, UTIs (increased risk with catheterization), blood stream infections (associated with IV catheters), osteomyelitis, CNS (meningitis, encephalitis)
What are targets for tx in sepsis?
infection, hypotension - due to vasodilation and increased vascular permeability and volume depletion
reduced CO - due to reduced preload and/or reduced contractility
intravascular coagulation
hormonal alterations
The 3 Heads of Sepsis: hypotension, hypoperfusion, organ dysfxn
How is antibacterial therapy decided for sepsis treatment?
cultures taken before tx,, IV antibiotics should be given ASAP and within 1 hour for both sepsis and septic shock
empiric broad-spectrum to cover all likely pathogens based on risk fx
dose based on PK/PD,, consider source control and removal of infected intravascular access devices
empiric tx narrowed once pathogen identified, shorter durations of tx preferred over longer, daily assessment for de-escalation
Procalcitonin levels to support discontinuation of antibacterials if optimal duration unclear
What are the most common pathogens in sepsis?
Gram +: S. aureus, S. pneumoniae, Enterococcus spp
Gram -: E. coli, K. pneumoniae, P. aeruginosa
How is hypovolemia treated in sepsis?
fluid resuscitation,, this is a medical emergency so resuscitation should begin immediately
at least 30 mL/kg (IBW) of IV crystalloid be given within first 3 hours followed by re-assessment ⇒ monitor HR, BP, arterial O2 saturation, RR, urine output, temp
initial target of MAP >/= 65,, goal to normalize lactate (</= 2 mmol/L)
How is vasodilation and hypotension treated in sepsis?
vasopressor tx
norepinephrine first choice, may add vasopressin or epinephrine to meet target
use dopamine as alternative to norepinephrine in selected pt (ex. if low risk tachyarrhythmias or absolute or relative bradycardia)
if norepinephrine not available epinephrine or dopamine can be used
target: MAP >/= 65, normalized serum lactate </= 2 mmol/L
How is myocardial depression treated in sepsis?
inotropes
suggest dobutamine in pt with hypoperfusion despite adequate fluid and vasopressors
Dobutamine recommended if low CO ⇒ primarily a beta-stimulant, increases contractility and HR, few alpha-adrenergic effects
can either add dobutamine to norepinephrine or use epinephrine (also an inotrope) alone
How is the neuroendocrine portion of sepsis treated?
corticosteroids: not necessary if adequate fluid resuscitation and vasopressor tx able to restore BP
if refractory septic shock suggest IV - typically HC 200 mg/day
Glycemic control: septic pt often hyperglycemic ⇒ impaired neutrophil fxn, impaired wound healing, pro-coagulant effects, target of 8-10 mmol/L
