What are the key 2021 Surviving Sepsis Campaign recommendations for managing adult sepsis?

Surviving Sepsis Campaign 2021: Key Recommendations

Initial Recognition and Resuscitation (First Hour Bundle)

Administer broad-spectrum intravenous antibiotics within 1 hour of recognizing sepsis or septic shock; each hour of delay decreases survival by approximately 7.6%. 1, 2

• Obtain at least two sets of blood cultures (aerobic and anaerobic) before starting antibiotics, but never delay antimicrobial administration beyond 45 minutes to obtain cultures 1
• Use empiric therapy covering gram-positive organisms (including MRSA when risk factors exist), gram-negative bacteria (including Pseudomonas in healthcare-associated infections), and anaerobes for intra-abdominal or aspiration sources 1
• Add empiric antifungal coverage (e.g., echinocandin) in patients with immunosuppression, prolonged ICU stay, total parenteral nutrition, or recent broad-spectrum antibiotic exposure 1

Give at least 30 mL/kg of intravenous crystalloid within the first 3 hours of sepsis-induced hypoperfusion (this recommendation was downgraded from strong to weak in 2021). 1, 2

• Use balanced crystalloid solutions over normal saline 0.9% (new weak recommendation in 2021) 2
• Continue additional fluids while hemodynamic improvement is observed, guided by dynamic indices (pulse-pressure variation, stroke-volume variation) or static variables (arterial pressure, heart rate, urine output) 1

Hemodynamic Targets (First 6 Hours)

• Target mean arterial pressure (MAP) ≥ 65 mmHg in most adults; consider higher targets (70–85 mmHg) for patients with chronic hypertension 1
• Maintain urine output ≥ 0.5 mL/kg/hour 1
• Target central venous oxygen saturation (ScvO₂) ≥ 70% (or mixed venous O₂ saturation ≥ 65%) 1
• Measure serum lactate immediately at sepsis recognition and repeat within 6 hours if initially elevated; use lactate normalization as a resuscitation endpoint 1

Vasopressor Management

Norepinephrine is the first-choice vasopressor for persistent hypotension despite adequate fluid resuscitation. 1

• Start at 0.05–0.1 µg/kg/min and titrate to maintain MAP ≥ 65 mmHg 1
• Peripheral initiation of vasopressors is now recommended over delaying initiation to obtain central venous access (new weak recommendation in 2021) 2
• Add vasopressin 0.03 U/min to norepinephrine when additional MAP support is needed or to reduce norepinephrine dose; vasopressin should never be used as the sole initial vasopressor 1
• Introduce epinephrine as a third-line agent if MAP targets remain unmet despite norepinephrine plus vasopressin 1

Source Control

• Identify or exclude a specific anatomic infection source requiring emergent intervention within 12 hours of septic shock onset 1
• Perform definitive source-control procedures (drainage, debridement, removal of infected devices) as soon as medically and logistically feasible 1

Antimicrobial Stewardship

• Reassess antimicrobial therapy daily once pathogen identification and susceptibility results are available, typically within 48–72 hours 1
• De-escalate to the most appropriate single agent within 3–5 days based on culture data and clinical improvement 1
• Plan a total antibiotic course of 7–10 days for most serious infections associated with septic shock 1
• Extend duration for slow clinical response, undrained infection foci, Staphylococcus aureus bacteremia, fungal/viral infections, or immunodeficiency 1

Corticosteroid Management

Do not use intravenous hydrocortisone routinely in adult septic shock patients if adequate fluid resuscitation and vasopressor therapy restore hemodynamic stability. 3, 1

• Consider hydrocortisone 200 mg/day if hemodynamic stability cannot be attained despite adequate resuscitation (new weak recommendation for ongoing vasopressor requirement in 2021) 3, 2
• Do not use ACTH stimulation testing to identify patients who should receive hydrocortisone 3
• Taper hydrocortisone when vasopressors are no longer required 3
• Do not administer corticosteroids for sepsis in the absence of shock 3

Mechanical Ventilation for Sepsis-Induced ARDS

• Target tidal volume of 6 mL/kg predicted body weight (strong recommendation, grade 1A) 3, 1
• Maintain plateau pressures ≤ 30 cm H₂O in passively inflated lungs 3, 1
• Apply positive end-expiratory pressure (PEEP) to prevent alveolar collapse; use higher PEEP strategies for moderate-to-severe ARDS 3, 1
• Use prone positioning in patients with PaO₂/FiO₂ ratio ≤ 100 mmHg (or < 150 mmHg) in facilities experienced with this practice 3, 1
• Maintain head-of-bed elevation at 30–45 degrees to reduce ventilator-associated pneumonia risk 3, 1
• Use a conservative fluid strategy once tissue hypoperfusion is resolved in established ARDS 1, 4

Blood Product Management

• Transfuse red blood cells only when hemoglobin falls below 7.0 g/dL, targeting 7.0–9.0 g/dL (strong recommendation, grade 1B) 3, 1
• Higher thresholds are permissible in active myocardial ischemia, severe hypoxemia, acute hemorrhage, or ischemic heart disease 3
• Do not use erythropoietin for sepsis-associated anemia 3
• Do not give fresh-frozen plasma to correct laboratory coagulopathy without bleeding or planned invasive procedures 3
• Administer prophylactic platelets when counts are < 10,000/mm³ without bleeding; consider when < 20,000/mm³ with significant bleeding risk; target ≥ 50,000/mm³ for active bleeding, surgery, or invasive procedures 3

Interventions NOT Recommended

• Do not use intravenous immunoglobulins routinely 3
• Do not use antithrombin for treatment 3
• Avoid high-frequency oscillatory ventilation 1
• Do not use pulmonary artery catheters routinely for sepsis-induced ARDS 1

Weaning and Extubation Criteria

Mechanically ventilated sepsis patients should undergo regular spontaneous breathing trials when they meet five criteria: 4

1. Arousable mental status, able to follow commands and protect airway 4
2. Hemodynamically stable without vasopressors (this is a hard contraindication to extubation) 4
3. No new potentially serious conditions developing 4
4. Low ventilatory requirements (PEEP ≤ 8 cm H₂O) 4
5. Low FiO₂ requirements (≤ 40%) that can be safely delivered via face mask or nasal cannula 4

Long-Term Outcomes and Goals of Care (New Section in 2021)

Address goals of care as early as feasible, but no later than within 72 hours of ICU admission. 1, 2

• Screen for economic and social support needs and make referrals for follow-up where available (strong recommendation) 2
• Use shared decision-making in post-ICU and hospital discharge planning (strong recommendation) 2
• Reconcile medications at both ICU and hospital discharge (strong recommendation) 2
• Provide written and verbal information about sepsis and its sequelae in hospital discharge summary (strong recommendation) 2
• Provide assessment and follow-up for physical, cognitive, and emotional problems after hospital discharge (strong recommendation) 2

Key Changes from 2016 Guidelines

• Initial fluid resuscitation recommendation downgraded from strong to weak 2
• New weak recommendation for balanced fluids over normal saline 2
• New weak recommendation for peripheral vasopressor initiation 2
• New weak recommendation for corticosteroids when ongoing vasopressor requirement exists 2
• Entire new section on long-term outcomes and goals of care with 12 new recommendations 2, 5
• Increased emphasis on early recognition, stringent first-hour management, and global perspective 6, 5