Surgical Critical Care: SIRS & Sepsis

Systemic Inflammatory Response Syndrome (SIRS)

Definition

An Exaggerated & Proinflammatory Response to Stressors (Infection, Trauma, Surgery, Ischemia, etc.)
Objective Criteria: ≥ 2 of:
- Temperature > 38°C or < 36°C
- Heart Rate > 90 Beats per Minute
- Respiratory Rate > 20 Breaths per Minute
- Leukocyte Count > 12,000, < 4,000 or > 10% Bands

Pathophysiology

Initiated By: DAMP or PAMP Binding to TLR
- Damage-Associated Molecular Pattern (DAMP): On Damaged Tissue
- Pathogen-Associated Molecular Pattern (PAMP): On Foreign Pathogens
- Toll-Like Receptors (TLR): Present on Endothelium and Immune Cells
Most Potent Stimulus: Endotoxin (Lipid A) – Stimulates TNFα Release
Primary Mediators: IL-1 & TNFα
- Propagates Cytokine Pathway – Dissociation of NF-kB from its Inhibitor Induces Massive Release of Proinflammatory Cytokines (IL-6, IL-8 & Interferon-Gamma)
- Alters Coagulation, Induces Coagulopathy & Impairs Fibrinolysis with Microvascular Thrombosis & Increased Capillary Permeability
- Induces Release of Stress Hormones – Catecholamines, Vasopressin & RAAS Activation
Other Mediators:
- Activation of Prostaglandin & Leukotriene Pathway
- Activation of C3a-C5a Complement Pathway

Compensatory Anti-Inflammatory Response Syndrome (CARS)

An Exaggerated Response to SIRS in an Attempt to Maintain Immunological Balance
May Induce a Relative Immunosuppression – Increases Susceptibility to Infection, Promoting the Sepsis Cascade

Roger Bone Stages

Stage 1: Local Pro-Inflammatory Reaction at Site of Infection or Injury to Limit Injury & Prevent Spread
Stage 2: Early CARS to Maintain Immunologic Balance
Stage 3: SIRS Predominates Over CARS
Stage 4: CARS Becomes Excessive Inducing Relative Immunosuppression
Stage 5: Multiple Organ Dysfunction (MOD) from Dysregulation of SIRS & CARS

Modern Definitions (Based on “Sepsis-3”)

Sepsis: Life-Threatening Organ Dysfunction Caused by a Dysregulated Host Response to Infection
- Organ Dysfunction Defined by SOFA Score ≥ 2
Septic Shock: Sepsis, Hypotension & Lactate > 2 mmol/L
- Hypotension Defined as Requirement of Vasopressors to Maintain MAP ≥ 65 mmHg

Old Definitions No Longer Used (Based on “Surviving SEPSIS”)

Sequential Organ Failure Assessment (SOFA) Score

	PaO2/FiO2 Ratio	GCS	Hemodynamic Stability	Bilirubin	Plt	Cr or UOP
0	≥ 400	15	MAP ≥ 70 mmHg	< 1.2	≥ 150	< 1.2
+1	< 400	13-14	MAP < 70 mmHg	1.2-1.9	< 150	1.2-1.9
+2	< 300	10-12	Dopamine ≤ 5 ug/kg/min or Dobutamine Any Dose	2.0-5.9	< 100	2.0-3.4
+3	< 200 & Mechanically Ventilated	6-9	Dopamine > 5 ug/kg/min, Epinephrine ≤ 0.1 ug/kg/min or Norepinephrine ≤ 0.1 ug/kg/min	6.0-11.9	< 50	3.5-4.9 or UOP < 500 cc/d
+4	< 100 & Mechanically Ventilated	3-5	Dopamine > 15 ug/kg/min, Epinephrine > 0.1 ug/kg/min or Norepinephrine > 0.1 ug/kg/min	≥ 12	< 20	≥ 5.0 or UOP < 200 cc/d

Quick SOFA (qSOFA) Score

A Modified SOFA Score to Assist Identification of Early Sepsis
Associated with Prolonged ICU Stay, Poor Outcomes & Increased Mortality
Definition: ≥ 2 of:
- Systolic Blood Pressure ≤ 100 mmHg
- Respiratory Rate ≥ 22 Breaths per Minute
- Altered Mental Status (GCS ≤ 14)

In-Hospital Mortality

Pathophysiology

Impairs End-Organ Oxygen Utilization (Not from Impaired Perfusion)
- Oxygen Consumption Increased in Early Shock
- SVO2 Increased Due to Decreased Utilization
- Causes Multisystem Organ Dysfunction/Failure (MOD/MOF)
Hyperglycemia
- Early Hyperglycemia from Impaired Utilization of Insulin (Low Insulin Levels)
- Late Hyperglycemia from Insulin Resistance (High Insulin Levels)
Diffuse Vasodilation & Hypotension
- From Release of Nitric Oxide (NO), Prostacyclin & Impaired Secretion of Vasopressin
Pulmonary Edema – From Pulmonary Vascular Endothelial Injury & Increased Permeability
Inhibition of Normal GI Barriers Allowing Bacterial Translocation into Systemic Circulation
Other Effects:
- Acute Kidney Injury
- Liver Dysfunction
- Encephalopathy
Gram Negative Sepsis
- Gram Negative Organisms Have Outer Membranes
- Releases Lipid A (Lipopolysaccharide) – Endotoxin that Induces Septic Shock
- Most Common Organism: E coli

Treatment

Initial Treatment: IV Fluids & Broad-Spectrum Antibiotics
- IV Fluid Bolus: 30 cc/kg
If Hemodynamically Unstable After IV Fluid Bolus: Start Vasopressors
- Goal MAP ≥ 65 mmHg (Should Be Individualized to the Patient)
- Vasopressor Choice:
  - First Choice: Levophed
  - Second Choice: Vasopressin
  - Third Choice: Epinephrine
  - If Other Failing: Phenylephrine or Dopamine
If Still Hemodynamically Unstable on Vasopressors: Steroids
- Consider Early Use – Often Started if Adding a Second Vasopressor
- Do Not Need to Confirm Adrenal Insufficiency Before Starting
- *See Endocrine: Adrenal Insufficiency

Procalcitonin (PCT)

Pathophysiology:
- Procalcitonin is a Peptide Precursor of Calcitonin Normally Produced in C-Cells of the Thyroid at Low Levels (< 0.1 ng/mL)
- During Sepsis Extra-Thyroidal Production Occurs in Inflamed & Infected Tissues
  - Mostly in Neuroendocrine Cells of the Lung & Intestine
  - Triggered by Inflammatory Cytokines & Bacterial Endotoxins
Primarily Used as a Biomarker in Sepsis to Guide Antibiotic Therapy
- Often Described in the Management of Community-Acquired Pneumonia (CAP)
Likelihood of Bacterial Infection:
- ≤ 0.10 ng/mL – Very Unlikely
- 0.10-0.25 ng/mL – Unlikely
- 0.25-0.50 ng/mL – Likely
- ≥ 0.50 ng/mL – Very Likely
Monitoring Antibiotic Therapy:
- Stop Antibiotics: PCT < 0.25 ng/mL or Decreased by > 80% from Peak Level (If Peak Level > 5.0 ng/mL)
- Continue Antibiotics: PCT Remains > 0.25 ng/mL But Decreasing
  - Should Decrease by ≥ 30% Daily During Resolution of Sepsis
- Change Antibiotics: PCT Remains > 0.25 ng/mL & Not Decreasing
- *In Critically Ill Patients a Target of PCT < 0.50 ng/mL May Be Used – Baseline Levels Expected to Be Higher