Sepsis and Septic Shock Management

what results from poor circulatory status?

insufficient oxygen delivery (DO2) to meet oxygen consumption (VO2)

what is the classic definition of hypotension

SBP < 90 mmHg OR decrease by 40 mmHg from baseline OR MAP < 65

define sepsis

life threatening organ dysfunction caused by a dysregulated host response to infection

clinical organ dysfunction can be recognized by using what?

the Sequential Organ Failure Assessment (SOFA)

define septic shock

Subset of sepsis with profound circulatory, cellular and metabolic abnormalities. Requires vasopressors for MAP >/= 65 with serum lactate > 2 mmol/L in the absence of hypovolemia

what are the two main things involved in sepsis pathophysiology?

immune dysregulation and dysregulated vasculature

what immune dysregulation is seen in sepsis?

hyperinflammation + immunosuppression

what things play a role in immune dysregulation in sepsis?

how virulent and abundant the pathogen is and the hosts factors such as innate immune activation, relative immunosuppression, and maladaptive tolerance mechanisms

what happens in innate immune activation?

cytokine release

describe relative immunosuppression seen in sepsis

neutrophils are more numerous but relatively hypofunctional and development of lymphopenia

describe the maladaptive tolerance mechanisms

monocytes develop impaired cytokine release and high energy expenditure leads to metabolic failure causing depleted and/or hypofunctional immune cells

what happens to endothelium in sepsis?

Endothelium contains many receptors for inflammatory cell signalers (cytokines, chemokines, damage signals). Has quick and large response to sepsis inflammation (vasodilation)

what is the glycocalyx?

an endothelial protective barrier

what happens to the glycocalyx in sepsis?

it is shed which leaves the endothelial tissue exposed and easily damaged

What happens to the complement system in sepsis

over-activity leads to tissue damage and microvascular thrombosis

what happens when regulation of endothelial permeability is lost?

intravascular fluid leaks outside of vasculature (third-spacing)

what are the major impacts of dysregulated vasculature?

profound vasodilation and loss of circulating blood volume

what is qSOFA?

the rapid bedside score to identify sepsis

how to identify sepsis using qSOFA:

Patient has at least two of the following:

• SBP < 100 mmHg

• RR > 22 breaths/min

  • Altered mentation

what are the SIRS criteria to identify sepsis?

Patient has at least two of the following:

• temperature > 38.0 degrees Celsius or < 36.0 degrees Celsius

• HR > 90 beats/min

• RR > 20 breaths/min

• WBC count > 12 × 10^9/L or < 4 × 10^9/L

T/F: guidelines recommend against using any one screening tool exclusively to identify sepsis

true

what are the general septic shock treatments

correction of underlying cause (antibiotics, source control), fluid resuscitation, vasopressors, inotropes, corticosteroids

urgency of initiating antibiotics depends on _______________________

acuity of patient and likelihood of sepsis

when should blood cultures be drawn in sepsis patients?

prior to initiation of antibiotics as long as this does not delay initiation of antibiotics

T/F: delay in antibiotics in sepsis is associated with increased mortality

true

what are the harms of unnecessary antimicrobials?

allergic rxns, kidney injury, thrombocytopenia, C. difficile infections and antimicrobial resistance

T/F: empiric therapy should be narrowed once pathogen identification and sensitivities are established and/or clinical improvement is noted

true

what is the antibiotic timing for present or absent shock where sepsis is definite or probable?

administer antimicrobials immediately, ideally within 1 hour of recognition

what is the antibiotic timing if shock is present and sepsis is possible?

administer antimicrobials immediately, ideally within 1 hour of recognition

what is the antibiotic timing if shock is absent and sepsis is possible?

rapid assessment of infectious vs noninfectious causes of acute illness — administer antimicrobials within 3 hours if concern for infection persists

when should MRSA coverage be added?

if patients are at high risk for MRSA infections

what are patient specific risk factors for MRSA infections?

prior history of MRSA infection or colonization, recent IV antibiotic use, hx of recurrent skin infections or chronic wounds, presence of invasive devices, hemodialysis, recent hospital admissions, severity of illness

T/F: if a patient is high risk for multi-drug resistant (MDR) organisms, suggest using two gram negative agents for empiric coverage

true

what are the patient specific risk factors for multi-drug resistant organisms?

proven infection of colonization with resistant organisms within the preceding year, recent broad spectrum IV antibiotic use within previous 90 days, travel to highly endemic country within previous 90 days, local prevalence of antibiotic-resistant organisms, hospital acquired infections

what are the goals of fluid therapy?

increase SV, CO, and DO2

how should crystalloids be given?

30 mL/kg over 15-30 minutes followed by 10 mL/kg boluses as needed

T/F: fluid therapy should be guided by hemodynamic parameters and assessment of volume status

true

which fluids are crystalloids?

LR, NS, Plasma-lyte, Normosol-R

which fluids are colloids?

albumin, starches

what does Surviving Sepsis say about fluid therapy?

crystalloids are the fluid of choice for initial resuscitation and subsequent intravascular volume replacement

when can albumin be considered in addition to crystalloids?

patients who require substantial amounts of crystalloids

1L of crystalloids yields ___________ mL of intravascular volume

250

where does the remainder of crystalloid fluid distribute since ~250mL are put into intravascular volume?

distributes to extracellular space

facts regarding lactated ringers

lactate is metabolized rapidly and may produce hyponatremia (Na = 130 mEq/L)

facts regarding normal saline

May produce hypernatremia, hyperchloremia, and metabolic acidosis. Possible risk of AKI

what are the two concentrations of albumin and what are they for?

5% is used for fluid resuscitation

25% is used for fluid mobilization

1L of albumin = _____________ mL remains intravascular

500-1000mL

T/F: efficacy of albumin is equivalent to crystalloids but are more expensive

true

facts regarding Hetastarch (Hydroxyethyl starch 6%)

NOT recommended for resuscitation in septic shock — increased risk of mortality, AKI, and bleeding

role of blood products like PRBC and FFP

for Hgb < 7 mg/dL or active bleeding

when should vasoactive agents be initiated?

when MAP remains < 65 mmHg despite fluid administration

why should arterial lines be placed if possible during shock?

for more accurate blood pressure monitoring

what is generally required for administration of vasoactive agents?

a central venous catheter

T/F: short term peripheral administration of vasoactive agents can be done to allow for early initiation of vasopressors

true

which meds are vasopressors?

norepinephrine, epinephrine, dopamine, phenylephrine, vasopressin, angiotensin II

which meds are inotropes?

dobutamine and milrinone

role of vasopressors:

primarily increase BP by causing arterial constriction

role of inotropes:

increase cardiac output by increasing the force at which the heart contracts (inotropy)

what is the first-choice vasopressor?

norepinephrine

when can vasopressin be added?

if the patient has inadequate MPA while on norepinephrine since it has been shown to help reduce norepinephrine requirement

when can epinephrine be added to a patients regimen?

if bp goals are not achieved with norepinephrine and vasopressin

which vasopressor has increased risk of tachyarrhythmias and is generally inferior to norepinephrine as a first line vasopressor?

dopamine

T/F: dopamine has limited utility in septic shock

true

role of dobutamine

is added to treatment of shock when patients require cardiac output support

what is dobutamine often used for?

cardiogenic shock (pump failure) since it is a b1 agonist and has predominantly inotropic effects

role of angiotensin II in septic shock

reserved for refractory distributive shock (is approved for septic or other distributive shocks)

role of phenylephrine in septic shock

no mention in Surviving Sepsis Guidelines — used when tachycardia limits norepinephrine utility

if cardiac dysfunction with persistent hypoperfusion is present despite adequate volume status and blood pressure what can be done?

consider adding dobutamine or switching to epinephrine

________________ improves the physiologic response to sepsis

cortisol

why does cortisol improve the physiologic response to sepsis?

regulation of the pro-inflammatory state, inhibition of inducible nitric oxide synthase (iNOS), reverses adrenergic receptor desensitization, increases sodium and water retention (increases intravascular volume)

when would hydrocortisone or fludrocortisone be added to patient regimens?

added after poor response to fluids and vasopressors (aka refractory shock) —- usually added when patient is hypotensive despite increasing norepinephrine dose and/or initiation of vasopressin

T/F: steroids have not shown improved time to shock resolution or increase in vasopressor free days

false