Latest Sepsis Guidelines: Surviving Sepsis Campaign 2021
The most current sepsis management guidelines are the Surviving Sepsis Campaign 2021 recommendations, which emphasize immediate recognition, rapid antimicrobial therapy within one hour, early fluid resuscitation with at least 30 mL/kg crystalloid, and norepinephrine as first-line vasopressor support to achieve a mean arterial pressure ≥65 mmHg. 1, 2
Initial Recognition and Resuscitation (First Hour Bundle)
Administer broad-spectrum intravenous antibiotics within 60 minutes of sepsis or septic shock recognition—each hour of delay reduces survival by approximately 7.6%. 1, 2 The empiric regimen must cover gram-positive organisms (including MRSA when risk factors exist), gram-negative bacteria (including Pseudomonas aeruginosa in healthcare-associated infections), and anaerobes for intra-abdominal or aspiration sources. 1
Give at least 30 mL/kg of intravenous crystalloid within the first 3 hours of septic shock recognition, though this recommendation has been downgraded from strong to weak in 2021. 1, 2, 3 Balanced crystalloid solutions are now weakly recommended over normal saline 0.9%. 3
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, 2
Hemodynamic Targets (First 6 Hours)
Target mean arterial pressure (MAP) ≥65 mmHg in most adults; for patients with chronic hypertension, aim for 70-85 mmHg because their autoregulatory curve is shifted rightward. 1, 2
Maintain urine output ≥0.5 mL/kg/hour as a bedside marker of adequate renal perfusion. 1, 2
Target central venous pressure (CVP) 8-12 mmHg (or 12-15 mmHg if mechanically ventilated) to assess fluid responsiveness. 1, 2
Achieve central venous oxygen saturation (ScvO₂) ≥70% (or mixed venous O₂ saturation ≥65%) to confirm sufficient tissue oxygen delivery. 1, 2
Measure serum lactate immediately at septic shock recognition and repeat within 6 hours if initially elevated; use lactate normalization as a resuscitation endpoint. 1, 2
Vasopressor Management
Initiate norepinephrine as the first-line vasopressor when MAP remains <65 mmHg after adequate fluid resuscitation, starting at 0.05-0.1 µg/kg/min and titrating to maintain MAP ≥65 mmHg. 1, 2 A new 2021 weak recommendation supports peripheral initiation of vasopressors rather than delaying for central venous access. 3
Add vasopressin 0.03 U/min to norepinephrine when additional MAP support is required or to reduce norepinephrine dose; vasopressin should never be used as the sole initial vasopressor. 1, 2
Introduce epinephrine as a third-line agent if MAP targets remain unmet despite norepinephrine plus vasopressin. 1, 2
Add dobutamine (2.5-5 µg/kg/min) when myocardial dysfunction or persistent tissue hypoperfusion is evident despite adequate MAP and volume status. 1
Source Control
Identify or exclude a specific anatomic infection source requiring emergent intervention within 12 hours of septic shock onset. 1, 2 Perform definitive source-control procedures (drainage, debridement, removal of infected devices) as soon as medically and logistically feasible; inadequate source control is independently associated with increased mortality. 1, 2
Antimicrobial Stewardship
Reassess antimicrobial therapy daily once pathogen identification and susceptibility results are available, typically within 48-72 hours. 1, 2
De-escalate to the most appropriate single agent within 3-5 days based on culture data and clinical improvement; de-escalation is a protective factor for mortality. 1, 2
Plan a total antibiotic course of 7-10 days for most serious infections associated with septic shock. 1, 2 Extend duration for slow clinical response, undrained infection foci, Staphylococcus aureus bacteremia, fungal/viral infections, or immunodeficiency. 1, 2
Corticosteroid Management
Do not routinely administer intravenous hydrocortisone in adult septic shock patients who achieve hemodynamic stability with adequate fluid resuscitation and vasopressor therapy. 4, 2 The 2021 guidelines include a new weak recommendation for intravenous corticosteroids when there is ongoing vasopressor requirement despite adequate resuscitation—specifically hydrocortisone 200 mg/day. 4, 3
Do not use ACTH stimulation testing to decide whether a septic shock patient receives hydrocortisone. 4, 2
Taper hydrocortisone once vasopressor support is no longer required. 4, 2
Corticosteroids are not indicated for sepsis in the absence of shock. 4, 2
Mechanical Ventilation for Sepsis-Induced ARDS
Use a tidal volume of 6 mL/kg predicted body weight (strong recommendation, high-quality evidence). 4, 2
Maintain plateau pressures ≤30 cm H₂O in passively inflated lungs. 4, 2
Apply positive end-expiratory pressure (PEEP) to prevent alveolar collapse; employ higher PEEP strategies in moderate-to-severe ARDS. 4, 2
Use prone positioning in patients with PaO₂/FiO₂ ratio ≤100 mmHg (or <150 mmHg) in facilities experienced with this practice. 4, 2
Keep the head-of-bed elevated 30-45° to reduce ventilator-associated pneumonia risk. 4, 2
Implement a weaning protocol with regular spontaneous breathing trials when patients meet five criteria: arousable, hemodynamically stable without vasopressors, no new serious conditions, low ventilatory requirements, and low FiO₂ that can be safely delivered via face mask or nasal cannula. 4, 1
Blood Product Management
Transfuse red blood cells only when hemoglobin falls below 7.0 g/dL, targeting a range of 7.0-9.0 g/dL (strong recommendation). 4, 2 Higher thresholds are permissible in active myocardial ischemia, severe hypoxemia, acute hemorrhage, or known ischemic heart disease. 4, 2
Do not use erythropoietin for anemia associated with sepsis. 4, 2
Do not give fresh-frozen plasma to correct laboratory coagulopathy unless there is active bleeding or an invasive procedure planned. 4, 2
Give prophylactic platelets when counts are <10,000/mm³ without bleeding; consider transfusion when <20,000/mm³ with high bleeding risk; aim for ≥50,000/mm³ for active bleeding, surgery, or invasive procedures. 4, 2
Interventions Not Recommended
Do not use intravenous immunoglobulins routinely in adult patients with sepsis or septic shock. 4, 2
Do not use antithrombin for treatment of sepsis and septic shock. 4, 2
Do not routinely use pulmonary artery catheters for patients with sepsis-induced ARDS. 4, 2
Do not use β-2 agonists for treatment of sepsis-induced ARDS in the absence of specific indications such as bronchospasm. 4, 2
New 2021 Recommendations on Long-Term Outcomes
The 2021 guidelines include 12 new recommendations addressing post-sepsis care, with strong recommendations to screen for economic and social support, use shared decision-making in discharge planning, reconcile medications at ICU and hospital discharge, provide written and verbal information about sepsis sequelae, and assess for physical, cognitive, and emotional problems after hospital discharge. 3
Key Changes from 2016 to 2021
The 2021 update downgraded the initial 30 mL/kg fluid bolus from strong to weak recommendation, added weak recommendations for balanced fluids over saline and peripheral vasopressor initiation, clarified antimicrobial timing when diagnosis is uncertain, and introduced extensive post-sepsis care recommendations. 3 The shift reflects a move away from aggressive early interventions toward more nuanced, individualized resuscitation strategies while maintaining the critical importance of rapid antimicrobial therapy and source control. 5, 3