What are the diagnostic and therapeutic management strategies for sepsis?

Diagnostic and Therapeutic Management for Sepsis

Initial Recognition and Diagnosis

Immediately initiate the Hour-1 Bundle when sepsis is suspected, regardless of qSOFA score, as delays in treatment directly increase mortality. 1

Screening and Assessment

• Screen acutely ill, high-risk patients for sepsis using qSOFA criteria (altered mental status, systolic BP ≤100 mmHg, respiratory rate ≥22/min), but do not wait for a positive qSOFA to begin treatment—it has poor sensitivity (31-50%) and is a screening tool, not a diagnostic criterion. 1
• Formal diagnosis requires infection plus SOFA score increase ≥2 points, but treatment must begin before this confirmation is complete. 1
• Identify the infection source through thorough clinical examination focusing on respiratory, genitourinary, gastrointestinal systems, and skin/soft tissue—the most common sites. 2

Diagnostic Testing

• Obtain at least two sets of blood cultures (aerobic and anaerobic) before antimicrobial therapy, but do not delay antibiotics beyond one hour for this. 3, 1
• Measure lactate immediately upon sepsis recognition and remeasure within 2-4 hours if elevated (≥2 mmol/L) to guide resuscitation. 1
• Perform imaging studies promptly to confirm infection sources. 3

Antimicrobial Therapy

Administer IV broad-spectrum antimicrobials within one hour of sepsis recognition—each hour of delay decreases survival by approximately 7.6%. 4, 3, 1

Antibiotic Selection and Administration

• Use empiric broad-spectrum therapy covering all likely pathogens (bacterial, fungal, viral) based on suspected source and local resistance patterns. 3
• For septic shock, use combination therapy with at least two antibiotics of different classes targeting the most likely pathogens. 3
• For neutropenic patients or Pseudomonas aeruginosa bacteremia, combine an extended-spectrum β-lactam with either an aminoglycoside or fluoroquinolone. 5
• Administer adequate dosages intravenously; if IV access is delayed in children, give first doses intramuscularly, orally, or rectally. 4

Antimicrobial Stewardship

• Reassess antimicrobial therapy daily for potential de-escalation once culture results and clinical response are available. 4, 5
• Use procalcitonin levels to support shortening antimicrobial duration or discontinuing empiric antibiotics in patients with limited clinical evidence of infection. 4

Hemodynamic Resuscitation

Begin aggressive fluid resuscitation immediately with 30 mL/kg crystalloid bolus for hypotension or lactate ≥4 mmol/L, infused rapidly over 5-10 minutes. 1

Fluid Management

• Use crystalloids (either balanced crystalloids or normal saline) as the initial fluid of choice for resuscitation. 4, 3
• Continue fluid administration as long as hemodynamic factors improve based on dynamic (pulse pressure variation, stroke volume variation) or static (arterial pressure, heart rate, capillary refill, skin mottling) variables. 4, 1
• Consider albumin when patients require substantial amounts of crystalloids. 4
• Never use hydroxyethyl starches—they are contraindicated in sepsis. 4

Vasopressor Therapy

• Initiate vasopressors for persistent hypotension despite adequate fluid resuscitation, targeting mean arterial pressure (MAP) ≥65 mmHg. 4, 3, 1
• Use norepinephrine as the first-line vasopressor agent. 1, 6
• If hypotension persists, add vasopressin, followed by epinephrine if needed. 6
• Peripheral vasopressor administration through a 20-gauge or larger IV line is safe and effective when central access is not immediately available. 6

Inotropic Support

• Administer positive inotropes when cardiac failure persists (low cardiac index and mixed venous oxygen saturation) despite adequate volume expansion—this occurs in 10-20% of adult sepsis cases. 4

Corticosteroid Therapy

• Consider hydrocortisone or prednisolone for patients requiring catecholamines, particularly those with refractory septic shock not responding to vasopressor therapy. 4, 6

Source Control

Identify and control the infection source within 12 hours when feasible—do not delay surgical intervention or drainage procedures. 4, 1

Source Control Interventions

• Use the least physiologically invasive effective intervention (e.g., percutaneous drainage rather than surgical drainage of an abscess). 4
• Remove intravascular access devices promptly after establishing alternative vascular access if they are a possible infection source. 4
• Delay definitive intervention for infected peripancreatic necrosis until adequate demarcation of viable and nonviable tissues has occurred. 4

Respiratory Support

Oxygen and Ventilation

• Administer oxygen to achieve saturation ≥90% and position patients semi-recumbent or laterally. 4
• Use non-invasive ventilation for increased work of breathing or hypoxemia despite oxygen therapy. 4
• For mechanically ventilated patients with sepsis-induced ARDS, use lower tidal volumes (6 mL/kg ideal body weight) and limit plateau pressures to ≤30 cmH₂O. 4, 3
• Maintain head of bed elevation between 30-45 degrees to limit aspiration risk and prevent ventilator-associated pneumonia. 3

Metabolic and Supportive Management

Glucose Control

• Use a protocolized approach targeting blood glucose ≤180 mg/dL. 3
• Monitor blood glucose every 1-2 hours until values stabilize, then every 4 hours. 3

Blood Product Therapy

• Target hemoglobin between 8-9 g/dL for acute anemia, adjusting based on clinical tolerance and central venous oxygen saturation. 4

Additional Supportive Measures

• Minimize continuous or intermittent sedation in mechanically ventilated patients. 3
• Provide pharmacological or mechanical deep vein thrombosis prophylaxis. 4
• Resume oral food intake after resuscitation and regaining of consciousness. 4
• Initiate early mobilization and active weaning of invasive support. 4
• Consider renal replacement therapy for acute kidney injury. 3

Ongoing Monitoring

Perform frequent reassessment of vital signs, capillary refill, skin mottling, mental status, and urine output rather than relying solely on static measurements. 1

• Monitor lactate normalization as a marker of tissue hypoperfusion resolution. 1
• Ensure continuous observation and frequent clinical examinations of septic patients. 3
• Reassess fluid responsiveness dynamically rather than using static central venous pressure measurements. 1