06: Sepsis & Septic Shock

Question 1

List the criteria for systemic inflammatory response syndrome (SIRS).

Answer 1

• Temp > 38 or < 36
• HR > 90
• RR > 20 or pCO2 < 32 mmHg
• WBC > 12k or < 4k or >10% bands

NB: 2 or more SIRS criteria + infection = sepsis

Question 2

Trace the path of sepsis/septic shock.

Answer 2

1. Infection (inflammatory response to microorganisms or invasion of normally sterile tissues)
2. SIRS
3. Sepsis (infection + 2 or more SIRS criteria; fever, tachycardia & tachypnea)
4. Severe sepsis (organ dysfunction: hypotension, hypoxemia, hypoperfusion [lactic acidosis, oliguria, altered mental status = obtundation])
5. Septic shock (hypotension despite fluid resuscitation [BP < 90 or SBP > 40 mmHg], diminished tissue perfusion, inotropic or vasopressor agents)
6. Multiple Organ Dysfunction Syndrome (MODS) (altered organ function, homeostasis unmaintainable without intervention)

Question 3

What is the most common organism causing sepsis in the US?

Answer 3

Gram-positive bacteria (Strep pneumoniae, staph aureus, strep pyogenes).

Question 4

Describe the pathophysiology of endotoxins (lipopolysaccharide [LPS]) (sepsis mechanism I).

Answer 4

• Direct invasion; integral components of outer surface of organism has capacity to stimulate host cells, producing a stereotypic inflammatory response.
• Lipopolysaccharide (the endotoxin) is an essential component of the outer membrane of GNs.
• Because the structure is deep within the intact cell membrane, interaction with host tissue predominantly occurs during growth phase of the bacteria, during cell lysis by host clearance mechanism (e.g., complement fixation) or during cell lysis after an antibiotic action.
• Induces TNF and IL-1

NB: Teichoic acids (unique to GPs) may also stimulate inflammatory response in similar manner.

Question 5

Describe the pathophysiology of exotoxins (sepsis mechanism II).

Answer 5

• Certain strains of Staph aureus and Strep pyogenes (GAS) produce a group of TSSTs with the unique ability to act as superantigens.
• Unconventional binding to antigen-presenting cells and T lymphocytes.
• Novel binding permits very small amounts of these toxins to stimulate proliferation of large populations of T cells simultaneously, with the resultant production of large quantities of cytokines.

NB: Decreased protein C activity correlated with increased mortality (necessary for coagulation inactivation).

NB2: Inflammatory cascasde influences coagulation cascade, favoring coagulation (increased PAI-1 & TAFI)

Question 6

Describe the pathophysiology of shock.

Answer 6

• NO and ANP produced –> relax vasculature
• K channels open –> hyperpolarize membrane
• Vasopression rapidly depleted
• Early: CO is up, peripheral resistance down (patient warm and dry)
• Late: CO drops, peripheral resistance up
• (patient cold and clammy)

Question 7

Describe the basic principles of sepsis treatment.

Answer 7

The sepsis rescuscitation bundle:

• If lactate > 4 mmHg, give 20-30 ml/kg of IV fluid until CVP > 8 mmHg or lactate < 4 mmHg; repeat in 2-4 hours
• Send for blood, urine, sputum cultures
• Abx initiated within 1 hour of recognition; modify abx regimen accordingly
• Maintain SvO2 > 70%
• Administer fluids (NS, colloid, blood)
• Pressors if MAP < 65 or SBP < 90 mmHg (NE then vasopressin)

NB: Early Goal-Directed Therapy –> 16% mortality reduction (more fluid, blood & dobutamine [inotrope and vasodilator])

NB2: Neither insulin nor steroids work.

Question 8

What signs indicate acute organ dysfunction?

Answer 8

• Cardivascular: tachycardia, hypotension
• Renal: oliguria, anuria, incr. creatinine
• Respiratory: tachypnea (rapid breathing), PO2 < 70 mmHg, SO2 < 90%
• Hepatic: jaundice, incr. enzymes, decr. albumin, incr. PT
• Hemostasis: decr. platelets, incr. PT/APTT, decr. protein C, incr. D-dimer
• CNS: altered consciousness, confusion, psychosis
• Unexplained metabolic acidosis