Sepsis and Septic Shock Flashcards
Epidemiology
- ~ 2% of hospitalizations in developed countries
- 6-30% of intensive care unit patients
- Severe sepsis reported in 50-100 per 100,000 persons
- May account for > 34% of in-hospital deaths in United States
Pathophysiology
• Host immune system recognizes and responds to
presence of microorganisms in the body
• Host cells bind to Toll-like receptors and others on
microorganisms
• Triggers increased transcription of
• pro-inflammatory mediators (TNF-α, IL-1β),and
• anti-inflammatory cytokines (IL-10)
• These immunomodulatory cytokines activate neutrophils
which attack the offending microorganism
• Result: “overly exuberant inflammation”
• Activated neutrophils also injure endothelium
• Leads to release of mediators that ↑ vascular permeability
• Increased permeability leads to fluid loss to ‘third space’ (hypotension and edema)
• Activated endothelial cells release nitric oxide which causes profound vasodilation
• Vasodilation and intravascular fluid loss result in
***profound hypotension
Pathophysiology
what cascade is activated?
_________ lodge in small vessels and contribute to hypoperfusion and damage to tissues and organs
• Activated endothelium produces tissue factors and activation
of the clotting cascade
• Factor VIIIa → thrombin → fibrinogen to fibrin → binding of platelets = microvascular thrombi and disseminated intravascular coagulation (DIC)
• Microvascular thrombi lodge in small vessels and contribute to hypoperfusion and damage to tissues and organs
see slide 9
during a protective immune response which is depicted on the left hand side of this chart a balanced response entails a variety of pro-inflammatory reactions followed by a return to homeostasis by a set of compensatory mechanisms aimed at tempering the initial inflammation and tissue repair but if the pathogen succeeds in multiplying the immune response becomes unbalanced and harmful to the host (right hand side of chart), so host repsonse during sepsis characterized by concurrent hyperinflation (top of chart) and immunosuppressin (bottom)
pathophys
Vasodilation and increased vascular permeability and
fluid loss can lead to profound hypotension
• Profound hypotension and intravascular coagulation
contribute to:
Hypotension and intravascular fluid loss
• result in: reduced ______ and __________ lead to _______
hypoperfusion and damage to vital organs • Kidneys • Brain • Heart • Lungs • Liver
Hypotension and intravascular fluid loss
• result in reduced preload and
• along with tissue damage to the heart
• lead to reduced cardiac output
Myocardial depressants (nitric oxide and others)
• result in reduced myocardial contractility and
• reduced cardiacoutput
pathophys
summary
______ + ______ = hypotension
______ + ______ = reduced Cardiac Output and profound hypotension
increased clotting leads to formation of _______
• Increased Permeability + Reduced intravascular volume
= Hypotension
• Myocardial Depressants Produced (Nitric Oxide etc)
• Hypotension + Myocardial Depression = reduced Cardiac Output and profound hypotension
• Increased clotting leads to formation of Microthrombi
• Hypotension + Reduced Cardiac Output + Microthrombi = Profound Hypotension and Reduced Tissue Perfusion and End Organ Damage
Pathophysiology
what does poor tissue perfusion lead to?
• Poor tissue perfusion and reduced oxygenation
results in lactic acid production and acidosis
• Poor perfusion and intravascular coagulation result in
renal dysfunction and reduced urine output
• Poor perfusion, increased permeability, and intravascular coagulation result in acute pulmonary injury, pulmonaryn edema, and acute respiratory distress syndrome (ARDS), which also results in poor oxygenation and increasing acidosis
• Poor perfusion, increased permeability, and intravascularcoagulation result in reduced perfusion of the brain, confusion, delerium, loss of consciousness
Pathogenesis of Cardiovascular Deficiency
signs of hypoperfusion
serum lactate, bicarb
markers like C-reactive protein, BNP, interleukin B, endog protein C, endotoxin
Systemic Inflammatory Response Syndrome (SIRS)
• Old term for systemic response to a wide range of stresses
• Criteria included two or more of the following:
▫ Temperature > 38ºC or < 36ºC
▫ Heart rate > 90 bpm
▫ Respiratory rate > 20 breaths/min or PaCO2 < 32 mmHG
▫ WBC > 12 (or < 4) x 109
/L or > 10% immature (band) forms
Sepsis
old vs new definition
dont need to use SOFA score - predict morbidity rather than mortality
• The systemic response to infection
• Old definition: SIRS + proven or clinically suspected infection
▫ With exceptions of leukopenia and hypothermia, these changes are among the body’s normal systemic responses to infection and do not necessarily
imply a poor prognosis
• New definition more closely matches old definition of “severe sepsis”: ▫ Life-threatening organ dysfunction caused by a dysregulated host responseto infection. Organ dysfunction – acute change in total Sequential Organ Failure Assessment (SOFA) score ≥ 2 points
Quick SOFA (qSOFA) Criteria KNOW THIS
• May be used at bedside to identify patients likely to have prolonged ICU stay or to die in hospital • At least 2 of the following: ▫ Respiratory rate ≥ 22/min ▫ Altered mentation ▫ SBP ≤ 100 mmHg
if pt doesn’t have score of 2, can’t rule out sepsis
Severe Sepsis
• Old definition
• Sepsis associated with dysfunction of organ(s) distant from the site of infection, hypoperfusion, or hypotension • May include: ▫ Lactic acidosis ▫ Oliguria ▫ Acutely altered mental status ▫ Acute lung injury
similar to new def
Septic Shock
• Sepsis with hypotension that does not respond to adequate fluidresuscitation and requires vasopressor therapy
• Sepsis with circulatory, cellular, and metabolic dysfunction associated with higher risk of mortality than sepsis alone
• Patients require vasopressors to maintain mean arterial pressure (MAP)
≥ 65 mmHG and have serum lactate > 2 mmol/L (in the absence of hypovolemia)
Surviving Sepsis Campaign
Collaboration between
• European Society of Critical Care Medicine
• International SepsisForum
• Society of Critical Care Medicine
With the overall goal of more timely management of patients with sepsis or at risk of developing sepsis
Most Common Sources of Sepsis
• Pneumonia (most common cause, half of cases) • Intra-abdominal Infections • Urinary Tract Infections (increased risk with catheterization) • Blood stream infections (associated with IV catheters) • Osteomyelitis • CNS (meningitis, encephalitis) • In ~ 20-30% the source can not be found
Targets for Treatment
The Three Heads of Sepsis
Hypotension, Hypoperfusion, Organ Dysfunction
Infection Hypotension Due to • Vasodilation and increased vascular permeability • Volume depletion
Reduced Cardiac Output Due to • reduced preload and / or reduced contractility Intravascular coagulation Hormonal Alterations
need to treat infectious insult
Antibacterial Therapy
timing
• Effective antibacterials delivered within 1 hour
of diagnosis resulted in 79% survival
• For every additional hour antibacterials
are withheld there is 7.6% drop in survival
• Antibacterials withheld 9 -12h: survival ↓ to 25%
• Cultures should be taken before antimicrobial therapy
• IV antimicrobials should be given as soon as possible
and within 1 hour for both sepsis and septic shock
• Empiric broad spectrum antimicrobials to cover all
likely pathogens (bacterial and potentially fungal) based on risk factors
• Dosing based on PK/PD principles
• Consider source control and removal of infected
intravascular access devices
avoid recent use of ABX in last 3 months
Antibacterial Therapy
daily assessment for?
______to support discontinuation of antibacterials if optimal duration of therapy is unclear
• Empiric therapy narrowed once pathogen identified
• Shorter durations of therapy preferred over longer durations
o Optimal duration depends on many factors, including host, microbe, drug, and anatomical site
• Daily assessment for de-escalation of antimicrobial therapy
• Procalcitonin levels (in conjunction with clinical evaluation) to support discontinuation of antibacterials if optimal duration of therapy is unclear (not widely avail in AB)
Antibacterial Choice\
which are common organisms?
Blood cultures typically
• positive in only 1/3cases
• in up to 1/3 of cases cultures from all sites are negative
Patients with severe sepsis and positive cultures
• 62% Gram negative organisms
• 47% Gram positive
• 19% fungi
Most common Gram positive organisms
• Staphylococcusaureus
• Streptococcuspneumoniae
• Enterococcus spp
Most common Gram negative organisms • Escherichia coli • Klebsiella pneumoniae • Pseudomonasaeruginosa Antibacterial therapy is directed at the suspected source
if it’s sepsis of unknown source and
they have septic shock then a
carbopenum annd vanco typically be recommended
source control such as surgical drainage of abscess, debridement of necrotic aterial
Fluid Resuscitation
for hypovalemia
• Sepsis and septic shock are medical emergencies,
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 oxygen saturation, RR, urine
output, temperature
• Initial target of MAP ≥ 65 mmHg (drives pressure of tissue perfusion)
• Goal to normalize lactate (≤ 2mmol/L)
after additional fluids are guided by reassess of hemodynamic status
vasodilation
if sepsis is still not responding, vasopressor indicated
Vasopressor Therapy
• Norepinephrine (Levophed®) first choice as vasopressor
• May add vasopressin or epinephrine to meet target
• Use dopamine as alternative to norepinephrine in selectedpatients (e.g., if low risk tachyarrhythmias or absolute orrelative bradycardia)
- dopamine for compromised systolic fxn but causes more tachycardia (more erythrogenic than NE)
• If norepinephrine not available, epinephrine or dopamine can be used as alternatives (watch for arrythmias) –> more AE with E than NE
low doses of vasopressin may raise BP
Target
Mean Arterial Pressure ≥ 65 mm Hg
Normalized serum lactate < 2mmol/L
AE of NE
peripheral Ischemia Due to Norepinephrine
Norepinephrine is a profound vasoconstrictor
primarily an α-agonist with some β-agonist properties
high alpha vasoconsticting fx
dark limbs due to vasoconstiction
target myocardial depression
Inotropes
• Suggest dobutamine in patients with hypoperfusion
despite adequate fluid and vasopressor
• Dobutamine recommended if low cardiac output
• Primarily a β-stimulant
• Increases contractility and HR
• Few α-adrenergic effects
• Can either add dobutamine to norepinephrine or
use epinephrine (also an inotrope) alone
endocrine system
Corticosteroids
• Not necessary if adequate fluid resuscitation and
vasopressor therapy able to restore BP
• If refractory septic shock, suggest IV corticosteroids
• typically hydrocortisone 200 mg /day
Glycemic Control
• Septic patients often hyperglycemic → impaired neutrophilfunction, impaired wound healing, pro-coagulant effects, etc.
• Initial studies showed benefit of tight glycemic control of serum glucose (4 - 6 mmol/L)
• Largest study to date – NICE-SUGAR:
• tight glycemic control lead to increased rates of harm from hypoglycemia
• 2016 Blood Glucose Target ~10 mmol/L
(2021: 8-10 mmol/L) tight glycemic control led to increased rates of harm from hypoglycemia so now guidelines want 10mmol
Other Treatment
read
• Sedation and Analgesia
• Mechanical ventilation to improve oxygenation and
respiratory acidosis in acute respiratory distress syndrome
(ARDS) associated with sepsis
• Renal replancement therapy (dialysis) if required
• Bicarbonate therapy in patients with severe metabolic
acidemia with pH ≤ 7.2 and acute kidney injury
• Venous thromboembolism prophylaxis with low molecular
weight heparin or unfractionated heparin
• Stress ulcer prophylaxis if risk factors for GI bleeding
(proton pump inhibitor or H2-receptor blocker)
