Sepsis and Septic Shock

Sepsis = infection + organ dysfunction

Life-threatening organ dysfunction caused by dysregulated host response to infection

- SOFA score ≥2 with suspected or confirmed infection

- Leads to tissue damage, organ dysfunction, and death if untreated

Septic shock = Sepsis + elevated lactate + refractory hypotension

Subset of sepsis with circulatory and metabolic abnormalities

- Persistent hypotension despite fluids; requires vasopressors (MAP ≥ 65 mmHg)

- Serum lactate > 2 mmol/L after adequate resuscitation

> 2 mmol/L

Septic shock is sepsis with serum lactate > ____ mmol/L after adequate fluid resuscitation and refractory hypotension requiring vasopressors to maintain MAP > 65 mmHg

Staphlycococcus, Acinetobacter, Pseudomonas (SAP)

Which organisms are associated with higher mortality rates in sepsis due to multidrug resistance?

- Infants and older adults (> 65 years)

- COPD

- ESRD

- Diabetes

- Heart failure

- Liver cirrhosis

- Alcohol dependence

- Immunocompromised (e.g., chemotherapy, steroids, HIV)

- Invasive devices (e.g., catheters, ventilators)

Risk factors for sepsis

1. Disseminated Intravascular Coagulation (DIC)

- Microvascular thrombosis

- May lead to renal, pulmonary, or hepatic failure

2. Acute Respiratory Distress Syndrome (ARDS)

- Pulmonary dysfunction

- May progress to systemic inflammatory response (SIRS

- Results in severe hypoxia

3. Acute Kidney Injury (AKI)

- Occurs in up to 87% of septic patients

- Caused by decreased perfusion and O2 delivery

4. Hemodynamic Effects

- Decreased systemic vascular resistance (SVR)

- Increased cardiac output (CO)

Complications associated with sepsis

1. Leukocytosis or Leukopenia (WBC > 12,000 or< 4,000 cells/mm3)

2. Elevated lactate (> 2 mmol/L)

3. Serum Creatinine (> 0.5 mg/dL)

4. Acute oliguria (urine output < 0.5 mL/kg/hr)

5. Thrombocytopenia (PLT < 100,000/μL)

6. INR > 1.5 or aPTT > 60 secs

7. Hyperglycemia (PG > 140 mg/dL)

8. Hyperbilirubinemia (total bilirubin > 4mg/dL)

Laboratory signs of sepsis

1. Hyperthermia or Hypothermia: > 38 ◦C (100.4 ◦F) or < 36 ◦C (96.8◦F)

2. Tachycardia Heart Rate > 90 beats/min

3. Tachypnea: Respiratory Rate > 20 breaths/min orPaCO2 < 32 mmHg

4. Leukocytosis or Leukopenia: WBC > 12,000 cells/mm3 or WBC < 4,000cells/mm3

SIRS criteria

- If a person presents with at least 2 of the criteria, they are considered to be septic

1. AMS: GCS <14

2. Tachypnea: RR ≥ 22 breaths/min

3. SBP ≤ 100 mmHg

qSOFA criteria

- If a person presents with at least 2 of the criteria, they are considered to be septic

1. Measure lactate levels (remeasure in 2-4 hours)

2. Obtain blood cultures before administering antibiotics

3. Administer BROAD-spectrum antibiotics

4. Begin rapid IV fluid resuscitation

5. Start vasopressors if hypotensive

Sepsis 1-hour bundle

MAP = [(2 x DBP) + SBP]/3

How to calculate MAP?

↓ Serum lactate level back to normal

↑ Blood pressure (MAP > 65 mmHg)

Stabilize tissue hypoperfusion

Goals of fluid resuscitation

Crystalloid solutions 30 ml/kg IV within the first 3 hours

- Use balanced crystalloids [LR or Plasma-Lyte] over NS when possible

- D5W/D10W used as maintenance

Recommendations for fluid resuscitation

3 hours

Fluid resuscitation with crystalloid solutions (30 ml/kg) should be started within the first _____ hours.

less likely to cause acidosis

Why are LR and Plasma-Lyte preferred over NS for fluid resuscitation?

BROAD

- Piperacillin/Tazobactam (Zosyn) 4.5 g IV Q6H

- Cefepime (Maxipime) 2 g IV Q8H

- Meropenem (Merrem) 1 g IV Q8H

- Vancomycin (Vancocin) 15 mg/kg BID

Antimicrobial therapy for an undifferentiated type of infection.

1. Levofloxacin (Levaquin) 750 mg IV Q24

2. Ceftriaxone (Rocephin) 1-2 g IV QD + Azithromycin (Zithromax) 500 mg IV QD

3. Piperacillin/Tazobactam (Zosyn) 4.5 g IV Q6H

4. Cefepime (Maxipime) 2 g IV Q8H

5. Meropenem (Merrem) 1 g IV Q8H

6. Vancomycin (Vancocin) 15 mg/kg BID or Linezolid 600 mg IV Q12H

Antibiotics for sepsis as a result of pneumonia

1. Piperacillin/Tazobactam (Zosyn) 4.5 g IV Q6H

2. Cefepime (Maxipime) 2 g IV Q8H

3. Ertapenem (Invanz) 1 g IV Q24H

4. Meropenem (Merrem) 1 g IV Q8H

5. Vancomycin (Vancocin) 15 mg/kg BID

Antibiotics for sepsis as a result of a UTI

1. Vancomycin (Vancocin) 15 mg/kg BID +/- Piperacillin/Tazobactam (Zosyn) 4.5 g IV Q6H

2. Linezolid 600 mg IV Q12H

3. Daptomycin 4-8 mg/kg IV Q24H

Antibiotics for sepsis as a result of an SSTI

1. Ceftriaxone (Rocephin) 1-2 g IV QD + Metronidazole (Flagyl) 500 mg IV Q8-12H

2. Cefepime (Maxipime) 2 g IV Q8H + Metronidazole (Flagyl) 500 mg IV Q8-12H

3. Piperacillin/Tazobactam (Zosyn) 4.5 g IV Q6H

4. Ertapenem (Invanz) 1 g IV Q24H

5. Meropenem (Merrem) 1 g IV Q8H

Antibiotics for sepsis as a result of an IAI

- Zerbaxa: Ceftolozane/Tazobactam

- Avycaz: Ceftazidime/Avibactam

- Recarbrio: Imipenem-Cilastatin-Relebactam

- Vabomere: Meropenem/Vaborbactam

Combination antibiotics that cover MDR Pseudomonas

65 mmHg

Vasopressor therapy aims to achieve a MAP of ____ mmHg

septic shock

Vaspressors are indicated for patients with _____

- DOC: Norepinephrine (Levophed)

- Dopamine (Intropin)

- Vasopressin (Vasostrict)

- Epinephrine (Adrenaline)

- Angiotensin II (Giapreza

- BP is improving

- Urine output is improving

- Lactate levels going down

Within the first 3 hours of fluid resuscitation, check to see if what 3 things are improving?

- If they are not, then may have to administer vasopressors

Norepinephrine (Levophed) 0.01-0.3 mcg/kg/min

Stimulates beta-1 adrenergic and alpha adrenergic receptors which increase contractility, heart-rate, and vasoconstriction, which increases blood pressure and coronary blood flow

Dopamine (Intropin) 2-5 mcg/kg/min

Stimulates adrenergic and dopaminergic receptors, which produce a positive inotropic and chronotropic effect on the myocardium

Vasopressin (Vasostrict) 0.01 units/min

Stimulates V1 receptors, which increase systemic vascular resistance and mean arterial blood pressure

Epinephrine (Adrenaline) 0.05-2 mcg/kg/min

Stimulates beta and alpha adrenergic receptors, which cause vasoconstriction and increase blood pressure

Angiotensin II (Giapreza) 20 ng/kg/min

Synthetic human peptide hormone of the RAAS system that results in vasoconstriction and increased aldosterone release

Sepsis-induced hypoxemic respiratory failure or acute respiratory distress syndrome (ARDS).

What condition warrants the use of mechanical ventilation in septic patients?

A low tidal-volume ventilation strategy of 6 mL/kg

What tidal-volume strategy is recommended for patients with ARDS?

More than 12 hours per day (often continuous ventilation).

For moderate-to-severe ARDS, how long each day is ventilation typically required?

IV Corticosteroids: Hydrocortisone 200 mg/day

- role of use in septic shock is unclear

Which medication is initiated when both fluid resuscitation and vasopressor therapy are inadequate?

180 mg/dL

Current guidelines recommend initiating insulin therapy in patients after two BG measurements are > ____ mg/dL

- Monitor every 1-2 hours until glucose levels and insulin infusion rates are stable, then monitor every 4 hours

true

T/F: Patients who develop AKI due to sepsis may require either continuous or intermittent renal replacement therapy (RRT).

Low-molecular-weight heparin (LMWH) is preferred; unfractionated heparin (UFH) is an alternative.

What is the preferred pharmacologic option for DVT prophylaxis in septic patients without contraindications?

Intermittent pneumatic compression (IPC) and/or graduated compression stockings (GCS).

What is recommended for DVT prophylaxis in patients who cannot receive heparin?

H₂ receptor antagonists (H2RAs) and proton pump inhibitors (PPIs).

Which two drug classes are used for stress ulcer prophylaxis in patients with sepsis or septic shock who have risk factors for GI bleeding?

false; PN alone OR in combo with EN is NOT recommended; EN is preferred.

T/F: Parenteral nutrition is recommended for patients with sepsis