Sepsis and SIRS Quiz

Sepsis/SIRS and MOF

• Sepsis is defined as a systemic inflammatory response to an infection.
• SIRS (Systemic Inflammatory Response Syndrome) is the body's response to severe clinical insults, including infection, inflammation, and stress.
• SIRS is characterized by two or more of the following: body temperature greater than 38 degrees Celsius or less than 36 degrees Celsius, heart rate over 90 beats per minute, respiratory rate over 20 breaths per minute or partial pressure of carbon dioxide (PaCO2) less than 32 mm Hg, and white blood cell count greater than 12,000/cu mm or less than 4,000/cu mm.
• Infection is a microbial phenomenon characterized by an inflammatory response to microorganisms or invasion of normally sterile host tissue by those organisms.
• Bacteremia is the presence of viable bacteria in the blood.
• The relationship between sepsis and SIRS is that SIRS is a broader category (a systemic inflammatory response), whereas sepsis is a specific condition of SIRS in response to an infection.

Objectives

• The definitions of Sepsis and the Sepsis Syndromes.
• The factors that precipitate and perpetuate the Sepsis Cascade.
• The pathogenesis of Multiple Organ Dysfunction in Sepsis.
• Treatment options in Sepsis.

Levels of Clinical Infection

• Level I: Locally Controlled
• Level II: Locally Controlled, Leukocytosis
• Level III: Systemic Hyperdynamic Response
• Level IV: Oxygen metabolism becomes uncoupled
• Level V: Shock, Organ Failure

Stages in the Development of SIRS (Bone, 1996)

• Stage 1: Local environment produces cytokines in response to injury/infection.
• Stage 2: Small amounts of cytokines are released into the circulation.
• Recruitment of inflammatory cells
• Acute Phase Response, kept in check by anti-inflammatory mediators (IL-10, PGE2, antibodies, cytokine receptor antagonists.)
• Stage 3: Failure to control inflammatory cascade – loss of capillary integrity, stimulation of nitric oxide (NO) production, maldistribution of microvascular blood flow, and organ injury and dysfunction.

High Risk Patients for Sepsis and Dying

• Middle-aged, elderly individuals are at high risk.
• Post-operative and post-trauma patients are at high risk.
• Post-splenectomy patients are at high risk.
• Transplant recipients are at high risk.
• Immunocompromised patients are at high risk (e.g., alcoholics/malnourished, those with predisposing genes).
• Delayed antibiotic administration is a high risk factor.
• comorbidities such as AIDS, renal/liver failure, and neoplasms raise risk.

Clinical Signs of Sepsis

• Fever
• Leukocytosis
• Tachypnea
• Tachycardia
• Reduced vascular tone
• Organ dysfunction

Clinical Signs of Septic Shock

• Hemodynamic Alterations

  • Hyperdynamic State (“Warm Shock”)
    • tachycardia
    • elevated or normal cardiac output
    • decreased systemic vascular resistance
  • Hypodynamic State (“Cold Shock”)
    • Low cardiac output

• Myocardial Depression

• Altered Vasculature

• Altered Organ Perfusion

• Imbalance of O2 delivery and Consumption

• Metabolic (Lactic) Acidosis

Organ System Involvement

• Circulation: Hypotension, increased microvascular permeability, shock
• Lung: Pulmonary Edema, hypoxemia, Acute Respiratory Distress Syndrome (ARDS)
• Hematologic: Disseminated Intravascular Coagulation (DIC), coagulopathy
• GI tract: Stress ulcer, translocation of bacteria, liver failure, gastroparesis, ileus, cholestasis
• Kidney: Acute tubular necrosis, renal failure
• Nervous System: Encephalopathy
• Skeletal Muscle: Rhabdomyolysis
• Endocrine: Adrenal insufficiency

Sources of Sepsis (International Cohort Study) in Severe Sepsis and Septic Shock

• Respiratory (66, 53)
• Abdomen (9, 20)
• Bacteremia (14, 16)
• Urinary (11, 11)
• Multiple (not listed)
• Overall Mortality rate: 35%

Treatment of Sepsis

• Antibiotics: Initiate immediately when cultures are drawn. Severe sepsis requires broad-spectrum antibiotics. Empiric antifungal drugs for neutropenic patients, patients with DM or having chronic steroid use
• Early Aggressive Fluid Resuscitation
• Inotropes (Dopamine, vasopressin, norepinephrine) for BP support
• Source Control: Early recognition, surgical intervention if indicated, Aggressive supportive care in intensive care units
• Steroid therapy (if adrenal insufficiency)
• Activated protein C
• Ventilatory strategies
• Glycemic control
• Newer therapies

Identifying a Septic Focus

• History
• Physical Examination
• Imaging
• Cultures (Blood, Urine, Sputum, Abscess)

Investigations

• Basic: WBC, Platelets, Coagulation studies, Renal function, Glucose, Albumin, LFT, ABG
• Specific? Source: Urine, CXR, Blood Cultures, Biopsy

Differentiating Sepsis from Noninfectious SIRS

• Procalcitonin
• C-reactive protein (CRP)
• IL-6
• Protein complement C3a
• Leptin (not yet readily available for clinical practice)

Treatment of Hypotension

• Intravenous fluids (crystalloids vs. colloids): more than maintenance needs, replace fluid losses

• Goals of initial resuscitation

• Central venous pressure 8-12 mmHg

• Mean arterial pressure 65 mmHg

• Urine output .5 ml/kg/hr

• Pulmonary capillary wedge pressure exceeds 18 mmHg

Steroids

• Improved refractory hypotension
• Reduced Mortality by 10%
• 50mg hydrocortisone IV 6 hours.

Stress Hyperglycemia

• Decreased insulin release
• Increased release of hormones that counter insulin
• Increased insulin resistance
• Hyperglycemia reduces ability of neutrophils and macrophages to combat infection

Tight Glycemic Control

• Continuous Insulin Infusion
• Maintain serum glucose 80-110 mg/dL
• Decreased mortality, less renal failure

Failed Therapies

• High dose methylprednisolone
• Anti-endotoxin antibodies
• TNF antagonists (soluble TNF receptor)
• Ibuprofen

Mortality

• Sepsis: 30-50%
• Septic Shock: 50-60%

Key Take Home Points

• Recognize Sepsis early and determine severity.
• Early Antibiotics are critical to resolution of shock.
• Resuscitate severe Sepsis and septic shock
• Early Goal Directed Therapy