What is the treatment for septic shock?

Treatment of Septic Shock

The treatment of septic shock requires immediate administration of broad-spectrum antibiotics within one hour of recognition, aggressive fluid resuscitation with 30 mL/kg crystalloid for hypotension or lactate ≥4 mmol/L, and vasopressor therapy with norepinephrine as the first-line agent to maintain mean arterial pressure ≥65 mmHg. 1

Initial Resuscitation and Hemodynamic Support

Fluid Resuscitation

• Administer 30 mL/kg crystalloid (approximately 2L for average adult) for hypotension or lactate ≥4 mmol/L within the first hours 1, 2
• After initial bolus, further fluid administration should be guided by dynamic parameters, clinical condition, and echocardiography 2
• Both balanced crystalloids and normal saline are reasonable options for resuscitation 3

Vasopressor Therapy

1. First-line: Norepinephrine to maintain MAP ≥65 mmHg 1, 3
2. Second-line: Add vasopressin (up to 0.03 U/min) to decrease norepinephrine requirements 1, 3
3. Third-line: Add epinephrine if target MAP is not achieved with above measures 1, 3
4. Dopamine should only be used in highly selected patients with low risk of tachyarrhythmias 1
5. Place arterial catheter as soon as practical for patients requiring vasopressors 1
   • Vasopressors can be safely administered through a peripheral 20-gauge or larger IV line if central access is delayed 3

Antimicrobial Therapy

Timing and Selection

• Administer broad-spectrum antibiotics within the first hour of recognizing septic shock 1, 3, 2
• Select antibiotics with activity against likely pathogens and good penetration into the presumed source 4

Recommended Regimens

• Moderate risk patients: Monotherapy with meropenem, imipenem/cilastatin, piperacillin/tazobactam, or ceftazidime 1
• High-risk patients: Combination therapy with antipseudomonal beta-lactam plus aminoglycoside 1
• Consider adding vancomycin if suspected catheter-related infection, known MRSA colonization, skin/soft tissue infection, or hemodynamic instability 1
• Administer beta-lactam antibiotics as prolonged or continuous infusion after an initial loading dose 2

Pathogen-Specific Therapy

• E. coli: Third-generation cephalosporins or piperacillin/tazobactam 1
• S. aureus: Vancomycin for 4-6 weeks 1
• Candida species: Amphotericin B or fluconazole for susceptible strains 1
• Carbapenem-resistant Klebsiella: Newer agents like ceftolozane/tazobactam, ceftazidime/avibactam, or meropenem-vaborbactam 1

Duration and De-escalation

• Typical duration: 7-10 days 1, 4
• Reassess antimicrobial regimen daily for potential de-escalation based on culture results and clinical improvement 1, 5
• Consider procalcitonin levels to guide discontinuation of antibiotics 1, 2

Source Control

• Identify and control the source of infection within 12 hours 1
• Remove infected catheters or devices 1
• Surgical intervention may be necessary for abscesses, infected necrotic tissue, or other controllable sources 2

Adjunctive Therapies

Corticosteroids

• IV hydrocortisone 200 mg/day as continuous infusion only for septic shock not responsive to adequate fluid resuscitation and vasopressor therapy 1, 3
• Taper when vasopressors are no longer required 1
• Consider combination of hydrocortisone and fludrocortisone for refractory septic shock 3

Blood Product Administration

• Transfuse RBCs only when hemoglobin <7.0 g/dL (target 7.0-9.0 g/dL) once tissue hypoperfusion has resolved 1
• Administer platelets prophylactically when counts <10,000/mm³ without bleeding, <20,000/mm³ with significant bleeding risk, or ≥50,000/mm³ for active bleeding, surgery, or invasive procedures 1

Ventilator Management (if needed)

• Target tidal volume of 6 mL/kg predicted body weight 1
• Maintain plateau pressures ≤30 cm H2O 1
• Apply PEEP to avoid alveolar collapse 1
• Consider prone positioning for PaO2/FiO2 ratio ≤100 mm Hg 1
• Elevate head of bed to 30-45 degrees 1

Monitoring and Assessment

• Target resuscitation goals: MAP ≥65 mmHg, improved mental status, normalized capillary refill time, decreasing lactate, and urine output ≥0.5 ml/kg/h 1, 3
• Perform daily assessment of clinical improvement, hemodynamic stability, inflammatory markers, and organ function 1
• Patients showing ongoing signs of infection beyond 7 days warrant diagnostic investigation and multidisciplinary re-evaluation 1

Special Considerations

• Pregnancy: Do not withhold life-sustaining therapy. Hypotension associated with septic shock is a medical emergency that can be fatal if left untreated 6
• Elderly patients: Start at lower doses, considering decreased hepatic, renal, or cardiac function 6

Common Pitfalls to Avoid

• Delaying antibiotic administration beyond one hour of recognition
• Inadequate source control
• Excessive fluid administration after initial resuscitation
• Failure to de-escalate antibiotics based on culture results
• Using corticosteroids in sepsis without shock
• Continuing antibiotics beyond 7-10 days without clear indication