1. SEPTIC SHOCK and MODS
Chapter 23

2. Progression of Bacteremia
Infection
Bacteremia
Systemic Inflammatory Response System (SIRS)
Sepsis
Severe Sepsis
Septic Shock
Multiple Organ Dysfunction Syndrome (MODS)

3. Bacteremia and Septicemia
Bacteremia: presence of bacteria in the blood.
Septicemia: If the body’s defense mechanisms fail, bacteremia becomes septicemia (growth/replication of bacteria in the blood).
Exotoxins
Proteins released during bacterial growth
Enzymatic action towards cells (neurotoxins, pneumotoxins, enterotoxins, hemolysins)
Produce antibodies (antitoxins)
Endotoxins
Contained within the cell wall of gram-negative bacteria
Released when these bacteria are destroyed and/or during bacterial growth
Pyrogenic: pro-inflammatory and fever inducing
Increase vascular permeability
Cause vasodilation
Activate coagulation cascade

4. Systemic Inflammatory Response Syndrome
Criterion:
1) Temperature: >38 C (100.4 F) or <36 C (96.8 F)
2) Heart Rate: > 90 beats/min
3) Respiratory Rate: > 20 breaths per minute or CaO2 levels < 32 mmHg
4) White Blood Cell Count: > 12,000, <4,000, or Normal with >10% bands

5. SEPSIS
(2) or more SIRS criterion present accompanying septicemia (bacterial, viral, or fungal)
Systemic response to infection
Additional Laboratory Abnormalities may be present:
Elevated C-reactive protein
Elevated serum procalcitonin
Hyperlactatemia
Hypoxemia
Elevated INR
Thrombocytopenia

6. SEVERE SEPSIS Sepsis associated organ dysfunction
Most commonly expressed by Hypotension
SBP < 90mmHg
MAP < 70
SBP decreased > 40 mmHg

7. SEPTIC SHOCK Severe Sepsis associated with persistent hypotension
Persistent hypotension (SBP <90mmHg) despite early fluid resuscitation efforts

8. MULTIPLE ORGAN DYSFUNCTION
Clinical Manifestations: Pulmonary: dyspnea, refractory hypoxemia, crackles, diminished breath sounds, respiratory acidosis. Renal: increased creatinine and BUN levels, oliguria (<0.5 ml/kg/hr), anuria. Hepatic: increased bilirubin, AST, ALT levels, Increased ammonia levels, jaundice, abdominal distention, muscle wasting, abdominal tenderness Gastrointestinal: paralytic ileus, hemorrhage, decreased bowel sounds, abdominal pain, constipation, diarrhea, anorexia, vomiting. Hematological: thrombocytopenia, disseminated intravascular coagulation. Cardiac: tachycardia, decreased SVR, increased oxygen consumption, decreased cardiac output. Neurological: lethargy, disorientation, agitation, restlessness, coma. Metabolic: muscle wasting, weight loss, hyperglycemia.

9. Inflammatory Mediators
Interleukin-1B
Released by macrophages and lymphocytes
Cause fever, vasodilation, hypotension, edema, myocardial depression, leukocytosis
Tumor Necrosis Factor
Released by macrophages, natural killer cells and mast cells as a response to interleukins
Platelet-Activating Factor
Released by phagocytes, platelets and endothelial cells
Cause increased clotting
Impedes tissue perfusion and oxygen extraction

10. Secondary Mediators Cytokines Prostaglandins Nitric oxide
I NOS  NO release
Vasodilation
Increased vascular permeability
Decreased cardiac contractility
Proteolytic enzymes

11. SEPTIC SHOCK What’s going on? Inflammation Hypoperfusion Decreased SVR
Decreased oxygen extraction by cells/tissues

12. Clinical Manifestations:
Tachycardia (compensatory mechanism)
Temperature instability (fever or low body temperature)
Tachypnea
Dyspnea
Confusion
Persistent hypotension
Cyanosis
Oliguria

13. Risk Factors: Age Pregnancy Suppressed immune system Major surgery
HIV, autoimmune diseases, cancer treatments
Major surgery
Long-term hospitalization DM
Malnutrition
External devices
Urinary catheters, endotracheal tubes, intravenous catheters

14. Treatment: identification of cause mechanical ventilation central venous catheter broad spectrum antibiotics fluid resuscitation vasopressors nutritional support insulin therapy to stabilize glucose levels corticosteroids DVT prevention stress ulcer prevention

15. Empiric Antibiotic Regimen
Vancomycin + Piperacillin/tazobactam (Zosyn) - Community Acquired
Vancomycin + Aztreonam
Tobramycin + Metronidazole
Vancomycin + Meropenum + Tobramycin - Hospital Acquired
Vancomycin + Aztreonam + Tobramycin + Metronidazole

16. Vancomycin
IV: treats systemic infections (MRSA infections of skin, bloodstream, endocarditis)
Oral: treats intestinal infections (c diff)
For sepsis treatment: 15mg/kg IV every 12 hours x days
Drug class: Glycopeptide Antibiotic
Gram Positive Bacteria are susceptible
Side effects:
ototoxic
nephrotoxic

17. Piperacillin/Tazobactam
Penicillin Antibiotic
For Sepsis: 3.375g IV every 8 hours, slow infusion over 4 hours
Gram positive and gram negative aerobic and anaerobic organisms
Side effects:
GI upset
Anxiety
Insomnia
Headache
Thrush/vaginal yeast infections

18. Aztreonam Monobactam Antibiotic
Gram Negative Bacteria (UTIs, Pneumonia, Septicemia, Peritonitis)
IV administration, IM injection, Nubulized
For Sepsis: 2g IV every 8 hours
Side effects:
GI distress
eosinophilia

19. Tobramycin Aminoglycoside Antibiotic Gram Negative (pseudomonas)
For Sepsis: 7mg/kg IV
Side effects:
Ototoxic
Nephrotoxic

20. Metronidazole
Anaerobic bacteria (positive and negative) and protozoans
Nitroimidazole
For Sepsis: 500 mg IV every 8 hours
Side effects:
Paresthesias
GI distress
Visual disturbances
Behavioral changes

21. Drug Class: Carbapenum Gram positive and negative bacterium
Meropenum
Drug Class: Carbapenum
Gram positive and negative bacterium
(febrile neutropenia, severe intraabdominal infections, meningitis)
For Sepsis: 1g IV every 8 hours
Side effects:
Chills
Confusion
Fainting
Tachycardia
Blurred vision
convulsions

22. Multiple Organ Dysfunction Syndrome
Results from uncontrolled and progressive inflammation
Defined as 2 or more organ systems failing
High mortality rate – 100% mortality rate if 5 or more organs are involved
Risk Factors:
Age
Major trauma
Severe burns
Preexisting chronic disease
Immunosuppression
Multiple blood transfusions
SEPSIS
Malnutrition

23. MODS Cells of Inflammation Neutrophils
Activate: free radicals, proteases, Platelet-activating factor, prostaglandins
Results in: endothelial damage, vasodilation, increased permeability, microvascular coagulation, selective vasoconstriction, hypotension, shock
Macrophages
Activate: TNR, IL-1
Results in: fever, anorexia, hyperglycemia, weight loss
Mast Cells
Activate: histamine, direct injury
Results in: vasodilation, increased vascular permeability, hypotension, shock

24. What’s Happening? Relative Hypovolemia (interstitial edema)
Hypoperfusion
Microvascular Clotting
Maldistribution of blood flow (shunting of blood)
Hypermetabolism (increased oxygen demand and depleted fuel for energy)
Tissue Hypoxia
Cellular Acidosis

25. Clinical Manifestations: Initial:
Low grade fever
Tachycardia
Dyspnea
Altered metal status
ARDS (s/s respiratory failure)

26. Days 7-10:
Liver Failure
Kidney Failure
Hepatic Encephalopathy

27. Days 14-24: GI dysfunction Bacterial translocation
Hematological failure
Cardiac Failure
Progressive
Initial: tachycardia, increased output
Late: bradycardia, profound hypotension, ventricular dysrhythmias
Worsening encephalopathy