31 Severe Sepsis and Septic Shock Minejima

Question 1

What is the definition of Sepsis?

Answer 1

Systemic Inflammatory Response Syndrome (SIRS) associated with a proven clinically suspected infection

Question 2

What is Systemic Inflammatory Response Syndrome (SIRS)?

Answer 2

The systemic response to a wide range of stresses. Two or more of the following: 1) Temp > 38 or < 36. 2) HR > 90. 3) RR > 20, or PaCO2 < 32. 4) WBC > 12,000 or < 4,000, or >10% immature bands

Question 3

What is the definition of “Infection”?

Answer 3

Inflammatory response to microorganisms. Invasion of microorganisms in a normally sterile site. Bacteremia = bacteria in blood

Question 4

What is the definition of Severe Sepsis?

Answer 4

Severe Sepsis = Sepsis (SIRS + Infection) + Organ dysfunction, hypoperfusion, or hypotension

Question 5

What is the definition of Septic Shock?

Answer 5

Sepsis with persistent hypotension despite fluid resuscitation; requires vasopressor therapy

Question 6

What is the definition of Multiple-Organ Dysfunction Syndrome (MODS)?

Answer 6

Presence of altered organ function requiring intervention to maintain homeostasis

Question 7

What is the etiology of Septic Shock?

Answer 7

Bacteria is the most common cause of septic shock. More Gram (+) cases of septic shock –> increased incidence in pneumonia and in the use of intravascular devices. More Gram (-) cases of death due to sepsis. Bacteremia is not necessary for the development of septic shock

Question 8

What is the Pathophysiology of Septic Shock?

Answer 8

Inflammation is essential to host response against infection. SIRS results from a dysregulation of the normal responses between proinflammatory and anti-inflammatory mediators. Pro-Inflammatory (TNF-a, IL-1, IL-6, IL-8) > Anti-Inflammatory (IL-1RA, IL-4, IL-10)

Question 9

What is the cascade of events that occur from infection?

Answer 9

Cytokine release –> inflammatory response (causes both a thrombotic response (coagulopathy) and inhibits fibrinolytic response (fibrin clots form))

Question 10

What are the signs and symptoms associated with Early Sepsis?

Answer 10

Fever or hypothermia. Rigors, chills. Tachycardia. Tachypnea. Nausea/vomiting. Hyperglycemia. Myalgias. Lethargy, malaise. Proteinuria. Hypoxemia. Leukocytosis. Hyperbilirubinemia

Question 11

What are the signs and symptoms associated with Late Sepsis?

Answer 11

Lactic acidosis. Oliguria. Leukopenia. DIC. Myocardial depression. Pulmonary edema. Hypotension (shock). Hypoglycemia. Azotemia. Thrombocytopenia. ARDS. GI hemorrhage. Coma

Question 12

What is Disseminated Intravascular Coagulation (DIC)?

Answer 12

Inappropriate activation of the clotting cascade (increased coagulation, decreased fibrinolysis) –> microvascular thrombi

Question 13

What is Acute Respiratory Distress Syndrome (ARDS)?

Answer 13

Loss of functional alveolar volume, impaired pulmonary compliance, profound hypoxemia

Question 14

What are the results of Multiple Organ Failure?

Answer 14

As the number of failing organs rise from 2 to 5, mortality increased from 54% to 100%

Question 15

What are the markers of Organ Dysfunction?

Answer 15

CNS (altered consciouness, confusion, psychosis). Respiratory (tachypnea, PaO2 < 70, SaO2 < 90%, PaO2/FiO2 < 250). Renal (oliguria ( 2)). Hepatic (jaundice, high bilirubin (> 2), high LFTs, low albumin). GI (ileus, GI bleed, acute pancreatitis, high amylase). Cardiovascular (tachycardia, hypotension, high CVP, high PAOP). Metabolic (Hyperglycemia, acidosis, high lactate, decreased lactate clearance). Hematological (low platelets ( 1.5, High aPTT, high D-dimer, low protein C)

Question 16

What is the Goal in the management of Sepsis?

Answer 16

Routine screening of seriously ill patients for severe sepsis to allow earlier implementation of therapy and improve outcomes. Hospital based performance improvement efforts in severe sepsis

Question 17

What should be done for the identification of causative infection?

Answer 17

Obtain blood cultures BEFORE antimicrobial therapy is initiated. Blood cultures (at least 2 sets, from different sites). Culture other sites as indicated. Perform 1,3 beta-D-glucan assay, mannan, and anti-mannan Ab assay if available and fungal infection is in differential. Perform necessary imaging studies to determine site of infection

Question 18

What is the outline for the initiation of empiric antibiotics?

Answer 18

Initiate antibiotics within the first hour of recognition of severe sepsis or septic shock. Include one or more drugs with activity against all likely pathogens (broad coverage). Should penetrate in adequate concentrations into the presumed source of sepsis. Reassess antimicrobial regimen on daily basis. Recently used antibiotics should be avoided. Suggest combination therapy. Combination therapy should not be administered for more than 3-5 days when used empirically (de-escalate to most appropriate single therapy as soon as susceptibility profile is known)

Question 19

What is Source Control like for Septic Shock?

Answer 19

Specific anatomic diagnosis of infection should be diagnosed or excluded within the first 6 hours. Evaluate for the presence of a focus of infection (drainage of abscess, debridement of necrotic tissue, removal of infected device)

Question 20

What is done when source control is required?

Answer 20

The effective intervention with least physiologic insult should be performed (i.e. percutaneous rather than surgical drainage of an abscess). Intravascular access devices which are potential sources of infection should be promptly removed

Question 21

What is the duration of therapy like for septic shock?

Answer 21

Recommended duration of therapy is typically 7-10 days (longer courses in patients with slow clinical response, undrainable foci of infection, or immunological deficiencies, including neutropenia). If the clinical syndrome is d/t noninfectious causes, stop antimicrobial therapy promptly

Question 22

What is Initial Resuscitation (Early Goal Directed Resuscitation)?

Answer 22

During the first 6 hrs of resuscitation, the goals of initial resuscitation of sepsis-induced hypoperfusion should include: Central Venous Pressure (CVP): 8-12mmHg. Mean Arterial Pressure (MAP): >65mmHg. Urine output > 0.5 ml/kg/hr. Central venous (superior vena cava) or mixed venous oxygen saturation > 70% or > 65%, respectively

Question 23

What is Initial Resuscitation with Fluid Therapy?

Answer 23

Give fluid challenges of 1,000 ml of crystalloids over 30 minutes (alternative 300-500ml of colloids). Crystalloids (normal saline, LR). Colloids (albumin). Reduce fluid administration rate if cardiac filling pressures increase without concurrent hemodynamic improvement

Question 24

What are Vasopressors?

Answer 24

May be required in some patients to achieve a minimal perfusion pressure and maintain adequate flow. Adequate fluid resuscitation should be ideally achieved before vasopressors or inotropes are used. Used in hypotension despite fluid challenge. Goal: MAP > 65

Question 25

What are the ADRs associated with Vasopressors?

Answer 25

Increased HR (increased myocardial O2 consumption), extravasation and local tissue damage, decreased splanchnic perfusion

Question 26

What are the Vasopressor agent (Inotropes) used?

Answer 26

Dopamine. Dobutamine. Norepinephrine. Phenylephrine. Epinephrine. Vasopressin

Question 27

What are the characteristics of Dopamine?

Answer 27

Increases MAP and CO (increased SV and HR). Useful in patients with systolic dysfunction. Dose-depended receptor effect

Question 28

What is the dosing of Dopamine like?

Answer 28

1-3mcg/kg/min - dopaminergic (do not use low dose for renal protection). 3-10mcg/kg/min - predominantly beta-1 agonist. > 10mcg/kg/min - predominantly alpha-agonist, some beta-1 agonist

Question 29

What are the characteristics of Dobutamine?

Answer 29

Dosed 2-40mcg/kg/min. Increased CO and decreased SVR. Inotrope > vasodilator > chronotrope

Question 30

What are the characteristics of Norepinephrine?

Answer 30

Potent alpha-adrenergic agent. Less pronounced beta-adrenergic activity. Increased MAP by vasoconstriction of peripheral vascular beds. Little change in SV or HR

Question 31

What are the characteristics of Phenylephrine?

Answer 31

Pure alpha-adrenergic, no effect on HR, decrease SV. Increased SVR and MAP

Question 32

What are the characteristics of Epinephrine?

Answer 32

Non-specific alpha- and beta-adrenergic. Unfavorable side effects: increase lactate level, tachycardia, etc. Reserve for patients who fail to respond to traditional therapies

Question 33

What are the characteristics of Vasopressin?

Answer 33

Stimulates V1a receptors. Low dose effective in raising BP in patients not responsive to other vasopressors. May be added to or substituted for norepinephrine up to 0.03 units/min

Question 34

What are the Vasopressor Recommendations?

Answer 34

Norepinephrine is the agent of choice to correct hypotension in septic shock. DA is alternative in select patients (low risk of arrhythmias, low HR). Epinephrine when additional agent needed to maintain BP. Phenylephrine not recommended except when: NE associated w/ serious arrhythmias, CO known to be high and BP persistently low, As salvage therapy). Low dose dopamine SHOULD NOT be used for renal protection. All patients initiated on vasopressor therapy must have an arterial line placed

Question 35

What are the ionotropic therapy recommendations?

Answer 35

Trial of dobutamine (up to 20mcg/kg/min) can be administered or added to vasopressor if: myocardial dysfunction (low CO or high filling pressures), ongoing hypoperfusion despite achieving adequate intravascular volume and MAP

Question 36

What is Hydrocortisone like for Septic Shock?

Answer 36

IV hydrocortisone may only be given to septic shock patients who are not responsive to fluid resuscitation and vasopressors: lack of clear improvement in mortality, downgraded form previous guidelines, hydrocortisone 200mg/day in 3-4 divided doses. ACTH stimulation test should NOT be used to identify those patients with septic shock who should receive hydrocortisone (> 9 mcg/dL increase in cortisol 30-60 mins after administration of ACTH)

Question 37

What are other steroids like for Septic Shock?

Answer 37

Avoid dexamethasone. Fludrocortisone as substitute therapy. Wean patient from steroid therapy once vasopressors are no longer required. Dose of corticosteroids comparable to > 200mg hydrocortisone daily should NOT be used in severe sepsis or septic shock. Corticosteroids should NOT be administered for the treatment of sepsis in the absence of shock (may use treatment if prior history of steroid use or adrenal insufficiency (stress dose))

Question 38

What is Blood Product Administration like for Septic Shock?

Answer 38

Once tissue hypoperfusion has resolved + no extenuating circumstances –> RBC transfusion should occur when Hgb decreases to < 7 g/dL (< 70 g/L): Target hemoglobin of 7-9 g/dL in adults, increase O2 delivery but not consumption. Erythropoietin should NOT be used as treatment for anemia associated with severe sepsis

Question 39

What is Blood Product Administration like when there is no bleeding or planned invasive procedures?

Answer 39

Fresh frozen plasma should not be used to correct clotting abnormalities (in severe sepsis platelets should be administered when counts are < 10,000 in the absence of bleeding). Antithrombin agents should not be administered

Question 40

What is the role of Activated Protein C?

Answer 40

Inhibits PAI-1 and TAFI (which usually suppresses fibrinolysis)

Question 41

What is the Recombinant Human Activated Protein C (rhAPC) that used to be used?

Answer 41

Drotrecogin alfa (Xigris). Dosed 24 mcg/kg/hr x 96hrs (infusion). No adjustment needed for renal dysfunction. Many contraindications and precautions (bleeding risk). VERY expensive. Taken off the market, no longer used

Question 42

What is Glucose Control like in Septic Shock?

Answer 42

Patients with hyperglycemia in the ICU should receive IV insulin therapy (Goal BG < 180). Patients receiving IV insulin should also be given a glucose source. BG levels should be monitored Q1-2h until insulin infusion rates are stable; then 4 hrs thereafter. Low glucose levels obtained with point-of-care testing should be evaluated with caution. These higher glucose goals are d/t the NICE SUGAR study

Question 43

What is Bicarbonate Therapy like in Septic Shock?

Answer 43

The use of sodium bicarbonate therapy for purpose of improving hemodynamics or reducing vasopressor requirements in patients with hypoperfusion-induced acidemia with pH > 7.15 is NOT recommended. Bicarb therapy has been associated with causing: Sodium and fluid overload, Increase in lactate and pCO2, Decrease in serum ionized calcium

Question 44

What is DVT Prophylaxis like in Septic Shock?

Answer 44

Patients should receive DVT prophylaxis with either: 1) Low-dose unfractionated heparin (UFH) administered BID or TID, or 2) Daily low-molecular weight heparin (LMWH). If there is a contraindication for heparin use, mechanical prophylactic devices should be used. Combination of both of the above may be used in very high risk patients. In very high risk patients, LMWH is superior to UFH

Question 45

What is Stress Ulcer Prophylaxis like in Septic Shock?

Answer 45

Administer H2 blocker or PPI to prevent upper GI bleed. Weigh the risk against increasing stomach pH –> development of VAP and C. difficile infection. Reevaluate for continued need for prophylaxis

Question 46

Summary: What does Sepsis represent?

Answer 46

A complex pathophysiology and cascade of events, characterized by systemic inflammation, coagulopathy and decreased fibrinolysis

Question 47

Summary: What has initial resuscitation with EGDT shown to do?

Answer 47

Decrease mortality in hospitalized patients

Question 48

Summary: What is the management of shock like?

Answer 48

Manage with appropriate fluids +/- vasopressor therapy is necessary for improvement of hemodynamic measures and to reduce organ dysfunction. Prompt initiation of antibiotics is imperative to positively affect patient outcome. rhAPC is no longer recommended in the treatment of severe sepsis. Other supportive measures should be undertaken to improve patient outcomes