Sepsis Overview and Management

Sepsis Overview

• Sepsis is a life-threatening condition caused by a dysregulated host response to infection.
• Septic shock is a subset of sepsis where circulatory and cellular/metabolic abnormalities significantly increase mortality. A pressor requirement is often necessary.
• Sepsis is distinct from bacteremia. Bacteremia is the presence of bacteria in the bloodstream whereas sepsis involves an inflammatory response to those bacteria.

Objectives

• Define sepsis and septic shock
• Identify and describe homeostatic mechanisms disrupted in sepsis.
• Explain cryptic shock and cytopathic hypoxia.
• Detail how inflammation and coagulation interact and contribute to sepsis.
• Outline clinical signs and basic treatment for sepsis.

Terminology

• Systemic Inflammatory Response Syndrome (SIRS) is characterized by a systemic response to infection or trauma indicated by elevated heart rate, respiratory rate, temperature, and white blood cell count (WBC).
• Multiple Organ Dysfunction Syndrome (MODS) is a condition in which multiple organs are affected due to an abnormal functioning associated with SIRS.

SIRS Criteria

• Criteria for diagnosing SIRS vary between species (e.g., dog, cat, and horse).
• Specific values for heart rate, respiratory rate, temperature, and leukogram are presented in a table for each species.

Current Definitions

• Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection.
• Organ dysfunction is assessed using the Sequential (or Sepsis-related) Organ Failure Assessment (SOFA) score (a score of 2 or greater). MEWS/NEWS scores (or 2 or more SIRS criteria) can also be used.

SOFA Score

• The SOFA score is a table listing different organ systems (respiration, coagulation, liver, cardiovascular, CNS, and renal) with severity grades 0–4 based on specific measurements for each system. These scores are used to assess organ system dysfunction in sepsis.

Current Definition: Septic Shock

• Septic shock is a subset of sepsis where underlying circulatory and cellular/metabolic abnormalities substantially increase mortality. Treating shock often requires intravenous fluid resuscitation and pressor agents (such as norepinephrine).

Organisms of Sepsis

• Gram-negative bacteria, gram-positive bacteria, aerobes/anaerobes, fungi, and protozoa are among the pathogens that can cause sepsis.

Conditions Associated with Sepsis

• Several conditions can lead to sepsis
  • Thoracic, abdominal and cutaneous conditions, and injuries are presented, including tissue injury, hypotension, ischemia, especially in the gastrointestinal tract, and immune compromise.

Infection and Host Responses

• Pathogens (e.g., lipotechoic acid, peptidoglycan, bacterial DNA, exotoxins, fungal cell walls, flagellin) trigger the immune system.
• Proinflammatory cytokines (TNF-α, IL-1, IL-6, IL-8, IFN-γ) are released, activating inflammation and coagulation processes.
• Simultaneously, anti-inflammatory cytokines (TGF-β, IL-4, IL-10, IL-13) are released, opposing the inflammatory response.
  • The balance between these pro- and anti-inflammatory cytokines can impact the severity of the host's response.

Disrupted Homeostatic Mechanisms

• Vasomotor tone, inflammatory and coagulation cascades, and microvascular changes are major disrupted mechanisms in sepsis.
  • Reduced vasomotor tone with systemic vasodilation is a hallmark of sepsis. Microvascular changes include endothelial dysfunction, reduced microvascular blood flow, and mitochondrial dysfunction.
  • Cryptic shock occurs when microcirculatory perfusion is decreased despite normal hemodynamic values.
  • Cytopathic hypoxia occurs when the mitochondria are unable to utilized oxygen leading to increased apoptosis and cell death.

Microvascular Changes

• Loss of vascular muscle autoregulation, microthrombi formation, leukocyte activation, changes in RBC (red blood cell) rheologic properties, endothelial cell dysfunction, disruption of the endothelial glycocalyx, and changes in capillary permeability.

Cryptic Shock

• A condition characterized by decreased microcirculatory perfusion despite normal blood pressure. These changes are due to vasodilation, microthrombi formation, and edema.

Cytopathology

• Mitochondrial dysfunction due to sepsis, resulting in insufficient oxygen utilization by cells

Clinical Signs of Sepsis

• Early sepsis may present with red mucous membranes, increased heart rate, brisk capillary refill time, and bounding pulses.
• Late sepsis may manifest as thready pulses, prolonged capillary refill time, pale/muddy mucous membranes, hypothermia, hypoglycemia, stupor/coma, and organ failure.
• Cats frequently present differently than dogs. Cats often exhibit pale mucous membranes, bradycardia, hypothermia, and abdominal pain in the context of sepsis.

Progression to MODS/MOFS

• Cardiovascular, respiratory, gastrointestinal, renal, liver, brain, and coagulation systems could be affected by the progression of sepsis to multiple organ dysfunction syndrome (MODS).

General Treatment for Sepsis

• Fluids, pressors/inotropes and broad-spectrum antimicrobial therapy.
• Treat the underlying source (cause) of the infection.
• Support organ system function to combat complications.

Fluid Resuscitation and Management of Hypotension

• First, aggressively resuscitate with fluids.
• Use crystalloids and/or synthetic colloids, followed by plasma based on coagulation abnormalities.

Refractory Hypotension

• If hypotension persists after adequate fluid resuscitation, use pharmacologic agents (e.g., norepinephrine, vasopressin, dopamine, or dobutamine).

Antimicrobial Therapy

• Obtain cultures if possible.
• Empiric therapy tailored to the specific site of infection; broader spectrum may be used until culture results are available. Consider 4-quadrant coverage.

Additional Medical Therapy

• Supplementation of electrolytes/glucose, and nutrition support.
• Blood product support.
• Management of pain, and respiratory issues.
• Maintain appropriate body temperature, hydration and overall care of the patient including bandages and catheter support.

Monitoring

• Monitor for decompensation, and recognize and address early signs of sepsis.
• Monitor vital signs (temperature, heart rate, respiratory rate, and respiration effort), mucous membrane color, capillary refill time, urine output, urine specific gravity, mentation, EKG, blood pressure, pulse oximetry, blood gases, CBC, chemistry panel, coagulation profile, and blood glucose. Early recognition and treatment are essential for positive outcomes.

Prognosis

• A substantial risk of mortality (over 50%) can be associated with sepsis. Many comorbidities/organ failures related to sepsis contribute to this risk.