Sepsis and Septic Shock: Definitions & Criteria

Definitions

• Sepsis involves a dysregulated host response to infection leading to acute organ dysfunction.
• Septic shock is a subset of sepsis with profound circulatory and cellular/metabolic abnormalities that substantially increase mortality risk.

Criteria for Sepsis and Septic Shock

• Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection.
• Clinical features of sepsis include signs of infection, altered mentation, tachypnea, hypotension, and hepatic, renal, or hematologic dysfunction.
• Sepsis criteria in 2016 (SEPSIS-3) involve suspected infection and an increase of ≥2 in the sepsis-related organ failure assessment (SOFA) score.
• Septic shock is a subset of sepsis with circulatory and cellular/metabolic abnormalities, leading to increased mortality risk.
• Clinical features of septic shock include signs of infection, altered mentation, oliguria, cool peripheries, and hyperlactatemia.
• Septic shock criteria in 2016 (SEPSIS-3) include suspected infection plus vasopressor therapy to maintain MAP ≥65 mmHg and serum lactate >2.0 mmol/L despite adequate fluid resuscitation.

Etiology

• Sepsis can arise from community-acquired or hospital-acquired infections.
• Pneumonia is the most common source.
• Intra-abdominal and genitourinary infections are also common sources.
• Gram-negative isolates account for 62% of cases.
• Gram-positive isolates account for 47% of cases.
• Fungi account for 19% of cases.
• Blood cultures are positive in only about one third of cases.
• Staphylococcus aureus and Streptococcus pneumoniae are common gram-positive isolates.
• Escherichia coli, Klebsiella spp., and Pseudomonas aeruginosa are common gram-negative isolates.

Risk Factors

• Predisposition to infection and the likelihood of developing acute organ dysfunction are risk factors.
• Common risk factors for increased infection risk include chronic diseases and immunosuppression.
• Other risk factors include progression from infection to organ dysfunction, health status, timeliness of treatment, age extremes, sex, and race/ethnicity

Clinical Manifestations

• Signs of infection and organ dysfunction may be subtle.
• Potential warning signs of sepsis should be noted.
• Persistence of organ dysfunction is a key indicator.
• Cardiorespiratory failure is a manifestation.
• Includes respiratory compromise and ARDS (hypoxemia and bilateral infiltrates).
• ARDS is classified by Berlin criteria (Mild: PaO2/FiO2 201-300, Moderate: PaO2/FiO2 101-200, Severe: PaO2/FiO2 <100).
• Kidney injury is a manifestation.
• Involves acute kidney injury, oliguria, azotemia, and increased serum creatinine levels.
• Neurologic complications can occur.
• Includes coma or delirium: Sepsis-associated delirium is a diffuse cerebral dysfunction due to the inflammatory response to infection.
• Additional manifestations include:
• lleus
• Increased aminotransferase levels
• Altered glycemic control
• Thrombocytopenia
• DIC (disseminated intravascular coagulation)
• Adrenal dysfunction
• Sick euthyroid syndrome

Diagnosis

• Recognising the signs of sepsis and septic shock is vital.
• Systolic BP <100 mmHg.
• Respiratory rate >22 is breaths per minute.
• Altered mental status.
• A qSOFA score of ≥2 points has a predictive value for sepsis.

Septic Shock Criteria

• Septic shock involves:
• The need for vasopressor therapy to elevate MAP to ≥65 mmHg.
• Serum lactate concentration >2.0 mmol/L after adequate fluid resuscitation.

Treatment and Management

• Early treatment with initial management bundle (within 3 hours) and completion of the management bundle is crucial.
• Subsequent treatment focuses on monitoring and support of organ failure, adjunct therapies, and de-escalation of care.

Early Treatment: Two Bundles of Care

• Initial management bundle (within 3 hours):
• Early administration of broad-spectrum antibiotics.
• Collection of blood cultures.
• Measurement of serum lactate levels.
• Management bundle to be completed (within 6 hours):
• Intravenous fluid bolus.
• Treatment with vasopressors for persistent hypotension or shock.
• Re-measurement of serum lactate levels.
• Delaying antibiotics increases mortality by 3-7% for every hour
• Early goal parameters for blood glucose is to maintain levels <180 mg/dL, not <110 mg/dL

Resuscitation

• Sepsis and septic shock are emergencies that should be treated immediately.
• Resuscitation with intravenous crystalloid fluid (30 ml/kg) should begin within the first 3 h.
• Saline or balanced crystalloids are suggested for resuscitation.
• Hemodynamic assessments may be considered if the diagnosis is not clear clinically.
• Resuscitation should be guided towards normalizing serum lactate levels when possible.
• The target mean arterial pressure is 65 mmHg in patients with septic shock requiring vasopressors.
• Norepinephrine is the first choice vasopressor.
• Vasopressin can be used to reduce the norepinephrine dose.
• Dopamine should be avoided except in specific situations.
• Dobutamine is suggested when patients show hypoperfusion despite adequate fluid loading and vasopressors.
• Red blood cell transfusion is recommended only when hemoglobin is <7.0 g/dL, in the absence of acute myocardial infarction, severe hypoxemia, or acute hemorrhage.

Hemodynamic Monitoring

• The target MAP is ≥65 mmHg.
• Higher MAP of 75-85 mmHg may be appropriate for preexisting hypertension.
• Serum lactate is used to guide hemodynamic resuscitation.
• Base Excess <(-3) is moderately predictive of hyperlactatemia.
• Pulmonary Artery Catheter is generally not recommended.
• Restrictive transfusion strategy (transfusion threshold of Hgb 7-8 g/dL) is recommended over a liberal strategy (Hgb 9-10 g/dL).

Respiratory Support

• A target tidal volume of 6 ml/kg of predicted body weight is recommended in sepsis-induced ARDS.
• Higher PEEP is used in moderate to severe sepsis-induced ARDS.
• Prone positioning and neuromuscular blocking agents for 48 h are suggested in severe ARDS
• If there is no evidence of tissue hypoperfusion, a conservative fluid strategy should be used, and routine use of a pulmonary artery catheter is not recommended.

ARDS Definition

• Acute Respiratory Distress Syndrome in within 1 week
• Bilateral opacities-not fully explained by effusions, lobar/lung collapse, or nodules
• Respiratory failure not fully explained by cardiac failure or fluid overload
• PaO2/FiO2 and levels based on mild, moderate and severe classifications and measurements

Bundle of Lung Protective Ventilation Strategy

• Low tidal volumes (6ml/kg) are vital - using predicted body weight
• Target PaO2 should be between 55 mmHg and 80 mmHg or peripheral 02 saturation between 88% to 95%.
• Plateau pressure should target <30cm.

General Supports

• We suggest early proning of at least 12 hours/day in severe ARDS
• Continuous or intermittent sedation should be minimized in mechanically ventilated sepsis patients, with titration targets used whenever possible.
• A protocol-based approach to blood glucose management should be used in ICU patients with sepsis, Continuous or intermittent renal replacement therapy is recommended
• Pharmacologic prophylaxis (unfractionated heparin or low molecular weight heparin) against venous thromboembolism
• Goals of care and prognosis should be discussed with patients and their families.

Supportive Therapy: Hydrocortisone

• Intravenous hydrocortisone can be administered as 50 mg bolus q6 hours or 200mg OD.
• The typical minimum duration of treatment is 4 days.

Prognosis

• Overall mortality rate is 20%.
• Survivors are at increased risk of death, impaired physical or neurocognitive function, mood disorders, and low quality of life.
• Readmission within 90 days after sepsis occurs in about 40% of cases.