Summary

The 2021 Surviving Sepsis Campaign guidelines provide updated international recommendations for management of adults with sepsis and septic shock, covering screening, initial resuscitation, infection control, hemodynamic support, ventilation, adjunctive therapies, and long-term outcomes. Notable updates from 2016 include a strong recommendation against qSOFA as a sole screening tool, favoring balanced crystalloids over normal saline, suggesting peripheral vasopressor initiation, prolonged beta-lactam infusion, restrictive RRT timing, and new emphasis on post-sepsis recovery, peer support, and follow-up.

Key Recommendations

Do not use qSOFA alone as a sepsis screening tool; use combinations such as SIRS, NEWS, or MEWS along with clinical assessment.
For sepsis-induced hypoperfusion or septic shock, give at least 30 mL/kg IV crystalloid within the first 3 hours, then guide further fluid by dynamic measures (passive leg raise, stroke volume variation, capillary refill).
Use balanced crystalloids as first-line resuscitation fluid; reserve albumin for patients receiving large crystalloid volumes; avoid hydroxyethyl starches and gelatins.
Target initial MAP ≥ 65 mm Hg in septic shock requiring vasopressors.
Administer antimicrobials immediately and within 1 hour for septic shock or high-likelihood sepsis; for possible sepsis without shock, complete rapid assessment and start antibiotics within 3 hours if concern persists.
Use norepinephrine as first-line vasopressor; add vasopressin when norepinephrine dose is 0.25–0.5 µg/kg/min, then add epinephrine if needed; add hydrocortisone 200 mg/day for ongoing vasopressor requirement of ≥ 0.25 µg/kg/min for ≥ 4 hours.
Initiate vasopressors peripherally (proximal to antecubital fossa) to avoid delay; transition to central access when feasible.
In ARDS, use low tidal volume (6 mL/kg PBW), keep plateau pressure ≤ 30 cm H2O, use higher PEEP in moderate-severe ARDS, and prone position > 12 hours/day for PaO2/FiO2 < 150.
Use prolonged (extended/continuous) infusion of beta-lactams after an initial loading dose, with PK/PD-guided dosing.
Transfuse RBCs using a restrictive threshold of hemoglobin < 70 g/L.
Start insulin when blood glucose ≥ 180 mg/dL, targeting 144–180 mg/dL.
Provide VTE prophylaxis with LMWH (preferred over UFH), stress ulcer prophylaxis in at-risk patients, and early enteral nutrition within 72 hours; do not routinely use IV vitamin C, IV immunoglobulins, or polymyxin B hemoperfusion.

Thresholds & Doses

Initial crystalloid resuscitation: ≥ 30 mL/kg IV within 3 hours of sepsis-induced hypoperfusion.
MAP target: ≥ 65 mm Hg in septic shock.
Antibiotic timing: within 1 hour for septic shock/probable sepsis; within 3 hours for possible sepsis without shock.
Vasopressin: fixed dose typically 0.03 U/min (up to 0.06 U/min); add when norepinephrine 0.25–0.5 µg/kg/min.
Hydrocortisone: 200 mg/day IV (e.g., 50 mg q6h or continuous infusion) when norepinephrine/epinephrine ≥ 0.25 µg/kg/min for ≥ 4 hours.
ARDS ventilation: tidal volume 6 mL/kg predicted body weight; plateau pressure ≤ 30 cm H2O; may reduce to 4 mL/kg if plateau exceeds 30.
Prone positioning: > 12 hours/day in ARDS with PaO2/FiO2 < 150.
RBC transfusion threshold: hemoglobin < 70 g/L.
Insulin initiation: glucose ≥ 180 mg/dL (10 mmol/L); target 144–180 mg/dL.
Conservative oxygen target (when applied): SpO2 88–92%, PaO2 55–70 mm Hg.
Source control: ideally within 6–12 hours of diagnosis.
Bicarbonate: consider in severe metabolic acidemia (pH ≤ 7.2) with AKIN stage 2–3.
Lactate: elevated > 2 mmol/L supports septic shock diagnosis; use to guide resuscitation toward normalization.

Citations

Screening and Early Treatment — qSOFA recommendation against as sole screening tool
Initial Resuscitation — 30 mL/kg crystalloid and MAP ≥ 65 mm Hg target
Infection / Time to Antibiotics — 1-hour and 3-hour antibiotic timing recommendations (Figure 1)
Hemodynamic Management / Vasoactive Agents — norepinephrine first-line, vasopressin addition, hydrocortisone trigger (Figure 2)
Ventilation / Protective Ventilation in ARDS — tidal volume 6 mL/kg, plateau ≤ 30 cm H2O, prone positioning
Additional Therapies / Corticosteroids — hydrocortisone 200 mg/day in septic shock with ongoing vasopressor need
Additional Therapies / RBC Transfusion Targets — restrictive threshold Hb < 70 g/L (TRISS, TRICC)
Additional Therapies / Glucose Control — insulin initiation at ≥ 180 mg/dL (NICE-SUGAR)
Long-Term Outcomes — goals of care, peer support, post-discharge follow-up, rehabilitation recommendations
Table 1 — Summary of recommendations and changes from 2016