Surviving Sepsis Campaign guidelines

Contents

Background

The Surviving Sepsis Campaign (SSC) began in 2002 as an international initiative to improve sepsis mortality through standardised evidence-based care bundles. SSC guidelines are updated periodically; the most recent full update was in 2021 (Evans, Crit Care Med 2021).

Sepsis-3 Definitions (Singer, JAMA 2016 — adopted by SSC)

  • Sepsis: life-threatening organ dysfunction (SOFA ≥2) caused by a dysregulated host response to infection
  • Septic shock: subset of sepsis with persistent hypotension (MAP <65 mmHg despite adequate fluid resuscitation) requiring vasopressors AND lactate >2 mmol/L despite resuscitation; hospital mortality >40%
  • qSOFA (quick SOFA): ≥2 of RR ≥22, GCS <15, SBP ≤100 — identifies high-risk patients outside ICU; poor sensitivity (not a diagnostic criterion)

Hour-1 Bundle (2018–2021)

The SSC 2018/2021 Hour-1 Bundle specifies five actions to complete within 1 hour of recognising sepsis or septic shock:

  1. Measure lactate — repeat if initial lactate >2 mmol/L
  2. Blood cultures — before administering antibiotics (if cultures do not cause delay)
  3. Broad-spectrum antibiotics — within 1 hour
  4. 30 mL/kg crystalloid — for septic shock or lactate ≥4 mmol/L; reassess fluid responsiveness
  5. Vasopressors — noradrenaline; if MAP <65 despite initial fluid

Controversy Around Hour-1 Bundle

  • The bundle collapses the original 3-hour and 6-hour bundles into a single 1-hour window
  • Critics argue: (1) the evidence for the 1-hour antibiotic window is derived from retrospective septic shock data (Kumar 2006) and may not apply to all sepsis; (2) a mandatory 30 mL/kg bolus ignores fluid responsiveness assessment; (3) the bundle may reduce quality of sepsis recognition (diagnosis rushed to meet 1-hour window)
  • In the UK, most centres target 1 hour for antibiotics in septic shock; 3 hours for sepsis without shock
  • Lactate-guided resuscitation (targeting normalisation of lactate) has stronger evidence than fixed fluid volumes

Fluid Resuscitation

2021 SSC Recommendations

  • 30 mL/kg IV crystalloid for septic shock (standard initial bolus)
  • Reassess after initial bolus: only continue fluids if patient remains fluid responsive (dynamic assessment recommended)
  • Balanced crystalloids preferred over normal saline — SMART trial (Semler, NEJM 2018): balanced crystalloid associated with reduced major adverse kidney events vs 0.9% NaCl in critically ill patients
  • Albumin: SSC 2021 suggests albumin may be used in addition to crystalloids if large volumes needed; no mortality benefit in ALBIOS/SAFE trials
  • Avoid starch solutions: hydroxyethyl starches → ↑ AKI risk (6S, CHEST trials)

Conservative vs Liberal Fluid Strategy

CLASSIC trial (Meyhoff, NEJM 2022): restrictive fluid strategy in septic shock (only fluid if strict indications) was non-inferior to standard therapy for 90-day mortality; restrictive strategy did not reduce days alive without organ support but demonstrated safety of a conservative approach. See septic shock management page.

Fluid Responsiveness Assessment

Dynamic predictors (PPV, SVV, PLR, end-expiratory occlusion) are superior to static filling pressures (CVP). SSC 2021 recommends dynamic assessment over static measures — stop fluids when patient is not fluid responsive.

Vasopressors

First-Line: Noradrenaline

  • Noradrenaline (norepinephrine): α₁ predominant; maintains MAP with minimal cardiac effects at standard doses; first-line recommendation
  • Target MAP: ≥65 mmHg (individualise upward in patients with chronic hypertension)
  • Evidence for higher MAP (>75 mmHg): SEPSISPAM trial showed no improvement in outcomes for targets >65 mmHg (possible benefit in chronic hypertension subgroup only)

Second-Line: Vasopressin

  • Vasopressin 0.01–0.03 units/min: added when noradrenaline >0.25 mcg/kg/min to spare catecholamines; renally protective properties in VANISH (less RRT initiation); no mortality benefit over noradrenaline alone

Third-Line Options

  • Adrenaline (epinephrine): β₁ + α₁; added for noradrenaline-refractory septic shock; ↑ lactate (confounds monitoring)
  • Angiotensin II (ATHOS-3): effective in catecholamine-refractory vasodilatory shock; see ATHOS-3
  • Dopamine: not recommended as first-line (more arrhythmias, no benefit vs noradrenaline — SOAP II trial)

Dopexamine

  • β₂ + weak β₁ + dopamine receptor agonist; mild inodilator; used historically for splanchnic protection — evidence lacking; not in current SSC recommendations

Corticosteroids

2021 SSC Recommendation

  • Hydrocortisone 200 mg/day IV (continuous infusion or divided doses) for vasopressor-dependent septic shock (on vasopressors for ≥4 hours)
  • Weak recommendation, low quality of evidence
  • Evidence: ADRENAL (no mortality benefit, faster vasopressor weaning); APROCCHSS (mortality benefit in vasopressor-dependent cortisol non-responders)
  • See Journal Club: CORTICUS and hydrocortisone page for full discussion

What SSC Does NOT Recommend

  • Steroids for sepsis without shock (no evidence)
  • Routine ACTH stimulation testing to guide steroid use
  • Dexamethasone for septic shock (lacks mineralocorticoid activity, crosses blood-brain barrier, different pharmacology)

Glucose and Nutrition

Glucose

  • Target: 6–10 mmol/L (110–180 mg/dL)
  • Tight control (4.5–6.0 mmol/L): harmful — NICE-SUGAR demonstrated ↑ 90-day mortality from severe hypoglycaemia
  • Monitor glucose every 1–2 hours when insulin infusion running

Nutrition

  • Early enteral nutrition (within 24–48 hours) preferred over parenteral if gut is functional
  • Avoid routine parenteral nutrition in the first 7 days if patient is well-nourished (EDEN, EPaNIC trials)
  • Caloric targets: avoid early hypercaloric feeding (overfeeding); target ~25 kcal/kg/day once past the acute phase

Stress Ulcer Prophylaxis

  • SUP-ICU trial: pantoprazole not shown to reduce mortality; reduced clinically significant GI bleeding but at potential risk of C. difficile
  • SSC 2021: PPI or H₂ blocker recommended for patients with sepsis/septic shock who have risk factors for GI bleeding (mechanical ventilation >48h, coagulopathy)

Ventilation in Sepsis

If ARDS Co-Exists

  • Low tidal volume: 6 mL/kg ideal body weight; max plateau pressure ≤30 cmH₂O
  • PEEP: titrated to oxygenation; avoid both atelectasis and overdistension
  • Prone positioning for severe ARDS (P:F <150): PROSEVA trial — see prone positioning page

Sedation

  • Minimise sedation: sedation reduces delirium; light sedation (CPOT score-guided) preferred
  • SPICE III: dexmedetomidine as primary sedative — no mortality benefit; more bradycardia and hypotension; not recommended as default
  • Propofol or midazolam for deeper sedation when needed; dexmedetomidine as adjunct to facilitate weaning or agitation

Neuromuscular Blockade

  • Early routine NMBA in ARDS: ACURASYS (2010) showed benefit; ROSE trial (2019) showed no benefit with improved background sedation practices
  • SSC 2021: no routine NMBA in ARDS unless required for ventilator dyssynchrony or prone positioning

Weaning

  • Daily spontaneous breathing trials (SBT) — T-piece or PSV trial
  • Early extubation preferred

Surviving Sepsis Campaign vs Practice Controversies

Topic SSC Recommendation Controversy
30 mL/kg bolus Yes (for septic shock) CLASSIC trial: conservative fluid safe; fixed bolus ignores responsiveness
Antibiotics within 1 hour Yes Specificity debated; over-broad antibiotic use
MAP ≥65 Yes SEPSISPAM: no benefit above 65 (except hypertensive subgroup)
Steroids Yes (vasopressor-dependent shock) ADRENAL vs APROCCHSS conflicting mortality results
Balanced crystalloids Suggested SMART trial: moderate, non-ICU-specific evidence

Viva Questions

1. Summarise the Surviving Sepsis Campaign Hour-1 Bundle and its evidence base.

The SSC Hour-1 Bundle (introduced 2018, retained in 2021) specifies five actions within 1 hour of sepsis recognition: measure lactate (and repeat if >2 mmol/L); obtain blood cultures before antibiotics; administer broad-spectrum antibiotics; give 30 mL/kg crystalloid bolus if septic shock or lactate ≥4 mmol/L; and start vasopressors if MAP remains <65 mmHg. The rationale: early antibiotics — each hour of delay in appropriate antibiotic administration is associated with ~7% mortality increase (Kumar 2006, retrospective study); early vasopressors and lactate-guided resuscitation have biological plausibility. Controversies: the 1-hour window was derived from retrospective septic shock data and may not apply uniformly to all sepsis presentations; a mandatory 30 mL/kg bolus bypasses assessment of fluid responsiveness (a more nuanced approach); and clinicians may feel pressure to "bundle-ise" diagnoses rapidly, potentially reducing diagnostic quality. In UK practice, the 1-hour antibiotic target for septic shock is widely adopted; the 30 mL/kg bolus with reassessment is applied but modified by clinical context. Lactate-guided resuscitation (targeting normalisation) is supported by stronger evidence than fixed-volume protocols.

2. What is the evidence for and against giving corticosteroids in septic shock?

Corticosteroids in septic shock: the evidence is mixed. The earlier CORTICUS trial (Journal Club) showed faster shock reversal but no mortality benefit and higher superinfection rates. ADRENAL (2018, n=3658) showed no 90-day mortality benefit with hydrocortisone 200 mg/day, but significantly shorter time on vasopressors. APROCCHSS (2018, n=1241) showed a mortality benefit in a more severely ill population with relative adrenal insufficiency. The SSC 2021 gives a weak recommendation for hydrocortisone in vasopressor-dependent shock — reflecting the consistent vasopressor-sparing benefit across all trials and the possible mortality benefit in the sickest patients. Arguments against: the mortality benefit is not consistently demonstrated; steroids increase hyperglycaemia, muscle weakness, and may worsen infection; the optimal patient population remains unclear. Arguments for: the vasopressor-sparing effect is real and reduces catecholamine toxicity; in the most severely ill patients the mortality signal from APROCCHSS is compelling. Current practice: hydrocortisone 200 mg/day in patients remaining vasopressor-dependent after adequate resuscitation. Do not use ACTH stimulation testing to guide the decision.

3. A patient with septic shock is on noradrenaline 0.4 mcg/kg/min and remains hypotensive (MAP 57). What are your next pharmacological steps?

I am treating noradrenaline-refractory septic shock. My priorities: (1) Ensure resuscitation is adequate — has adequate fluid been given? Is there evidence of ongoing haemorrhage, obstructive shock (PE, tamponade), or unrecognised source? Echo to assess ventricular function and fluid status. (2) Add vasopressin 0.03 units/min as a fixed dose adjunct (SSC recommendation; spares catecholamines; see VANISH); this often allows noradrenaline dose reduction. (3) If still refractory: add hydrocortisone 200 mg/day IV (vasopressor-dependent shock; likely relative adrenal insufficiency); this will also reduce noradrenaline requirements. (4) Consider adrenaline as third-line agent if MAP still inadequate despite vasopressin + hydrocortisone. (5) Consider angiotensin II (ATHOS-3 evidence) if catecholamine-refractory vasodilatory shock. (6) Identify any source of vasopressor resistance: metabolic acidosis (pH <7.1 worsens catecholamine sensitivity — consider bicarbonate cautiously); hypocalcaemia (ionised Ca²⁺ <1 mmol/L reduces vascular tone — give calcium); severe metabolic derangements. (7) Consider ECMO if refractory shock with potentially reversible cause.