ICU · Resuscitation
Septic shock: SSC 2021 integrated — hour-1 bundle, vasopressors, and outcomes
Also known as Septic shock · SSC 2021 · Sepsis hour-1 bundle · Septic shock management · Surviving Sepsis Campaign
Septic shock = sepsis (infection + organ dysfunction — SOFA ≥2) + VASOPRESSOR requirement (to maintain MAP ≥65) + SERUM LACTATE 2 mmol/L (despite adequate fluid resuscitation). MORTALITY: hospital mortality over 40% (Sepsis-3). HOUR-1 BUNDLE (SSC 2021 — all within 1 hour of recognition): (1) MEASURE lactate (if 2, repeat). (2) BLOOD CULTURES ×2 (before antibiotics if no significant delay). (3) ADMINISTER BROAD-SPECTRUM ANTIBIOTICS (within 1 hour — Seymour: each hour of delay in antibiotics raises the odds of in-hospital death, adjusted OR 1.04 per hour; Kumar: survival fell 7.6% per hour of delay after documented hypotension). (4) BEGIN FLUID RESUSCITATION (30 mL/kg crystalloid for hypotension OR lactate ≥4 — but GOAL-DIRECTED — CLASSIC/CLOVERS support restrictive — reassess — not blanket 30 mL/kg for all). (5) ADMINISTER VASOPRESSORS if hypotensive during/after fluids (target MAP ≥65 — noradrenaline first-line). ESCALATION: noradrenaline → add vasopressin (VANISH/VASST) → add hydrocortisone (ADRENAL) → consider methylene blue/angiotensin II (refractory). SOURCE CONTROL (within 6-12h — drain, debride, remove device). STEROIDS: hydrocortisone 200 mg/day (if vasopressor-dependent — ADRENAL — faster shock reversal). MORTALITY: hospital mortality over 40% (Sepsis-3 — the sickest ICU patients — each intervention matters).
Checked against its sources on 11 Sept 2026
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CICMFFICMEDIC
Red flags
- HOUR-1 BUNDLE: lactate, cultures, antibiotics, fluids, vasopressors — ALL within 1 hour
- Antibiotics within 1 hour — each hour of delay raises the odds of in-hospital death (Seymour adjusted OR 1.04/h; Kumar 7.6% survival loss per hour)
- MAP ≥65 target (SEPSISPAM — higher not better)
- Goal-directed fluids (CLASSIC/CLOVERS — restrictive not inferior — avoid overload)
- Vasopressor escalation: noradrenaline → vasopressin → hydrocortisone → methylene blue
- Source control within 6-12h (drain, debride, remove device)
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Meet the patient
A 65-year-old woman arrives in septic shock from a biliary source. She has had 30 mL/kg of balanced crystalloid, her MAP is 60 on noradrenaline 0.5 mcg/kg/min, and her lactate is 4.0 — vasopressor-dependent with lactate over 2, exactly the Sepsis-3 shock phenotype. The question is no longer whether she is septic — it is how far up the vasopressor ladder you climb before the pressure holds.[11]
Every step of that ladder is evidence-backed, and every step has a trial name the examiner will ask for. Noradrenaline first (SOAP II), vasopressin next (VASST, VANISH), hydrocortisone when the catecholamines are not enough (ADRENAL, APROCCHSS) — and source control, always, before you declare the patient refractory.[7][9][8][4][10]
Sepsis vs severe sepsis vs septic shock (Sepsis-3)
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| Category | Definition | Management priority | Mortality |
|---|---|---|---|
| Sepsis | Infection + organ dysfunction (SOFA ≥2 from baseline) | Antibiotics within 1h + source control | substantially lower than shock |
| Septic shock | Sepsis + vasopressor (MAP ≥65) + lactate >2 (despite fluids) | Hour-1 bundle + vasopressors + source control + ICU | hospital mortality over 40% (Sepsis-3) |
Septic shock hour-1 bundle and escalation
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- HOUR-1 BUNDLE (ALL within 1 hour of recognition) — (a) MEASURE LACTATE: baseline — if >2 mmol/L, repeat at 2-4h (trend — clearing = improving; rising = worsening). Lactate is a PERFUSION marker (anaerobic metabolism from hypoperfusion) + PROGNOSTIC (higher = worse). (b) BLOOD CULTURES ×2 SETS: before antibiotics (if no >45 min delay) — source: peripheral + from each lumen of vascular catheter (if line infection suspected). ALSO: sputum, urine, wound swab, CSF (if source suspected). (c) BROAD-SPECTRUM ANTIBIOTICS within 1 HOUR: (i) SSC 2021: STRONG recommendation — within 1 hour for HIGH LIKELIHOOD septic shock + high mortality risk. (ii) Seymour (2017, NEJM — 49,331 patients): longer time to the 3-hour bundle and to antibiotics → higher risk-adjusted in-hospital mortality (adjusted OR 1.04 per hour for each) — while faster completion of the initial fluid bolus did NOT change mortality (OR 1.01/h, NS). (iii) Kumar (2006, CCM): in septic shock, each hour of delay in effective antimicrobials after onset of persistent/recurrent hypotension → average 7.6% decrease in survival (Ferrer 2014: mortality rises steadily after the first hour of delay). (iv) EMPIRIC: cover ALL likely organisms — Gram-positive + Gram-negative + atypical (depending on source). (v) DOSING: LOADING dose (high — bactericidal — achieve therapeutic level rapidly). (vi) DE-ESCALATE at 48-72h (based on cultures — narrow to specific). (d) FLUID RESUSCITATION: 30 mL/kg crystalloid (SSC 2021 — for hypotension OR lactate ≥4) — BUT GOAL-DIRECTED: give boluses and reassess (urine output, BP, lactate, capillary refill, passive leg raise — Monnet meta-analysis: pooled sensitivity 0.85, specificity 0.91) — DON'T give 30 mL/kg blanket if not responsive. CLASSIC (2022, NEJM): ICU patients already given at least 1 L — restricting further IV fluid did NOT result in fewer deaths at 90 days than standard therapy (42.3% vs 42.1%). CLOVERS (2023, NEJM): restrictive early strategy (prioritise vasopressors, ~2.1 L less fluid) vs liberal — no significant difference in death before discharge home by day 90 (14.0% vs 14.9%). AVOID fluid overload (excess positive balance worsens outcomes). (e) VASOPRESSORS if HYPOTENSIVE (during/after fluids): noradrenaline first-line (target MAP ≥65). Can start PERIPHERALLY (large vein, forearm — monitor site — SSC 2021 accepts peripheral as initial). Goal: restore perfusion (MAP ≥65, lactate clearing, urine >0.5 mL/kg/hr)
- VASOPRESSOR ESCALATION (if MAP <65 despite fluids) — (a) NORADRENALINE first-line (alpha-1 — vasoconstriction + mild beta-1 — some inotropy; titrate to MAP ≥65). SOAP II (2010, NEJM — 1,679 patients): dopamine vs noradrenaline in shock — no significant 28-day mortality difference (52.5% vs 48.5%) but MORE arrhythmic events with dopamine (24.1% vs 12.4%, P<0.001) — noradrenaline preferred. (b) ADD VASOPRESSIN (V1 receptor — different pathway from catecholamines): VASST (2008, NEJM) — low-dose vasopressin (0.01-0.03 U/min) as an adjunct in patients already on at least 5 mcg/min noradrenaline: no overall 28-day mortality difference (35.4% vs 39.3%, NS; less-severe-shock stratum 26.5% vs 35.7%, P=0.05). VANISH (2016, JAMA) — early vasopressin (titrated up to 0.06 U/min) vs noradrenaline: no improvement in kidney failure-free days and no mortality difference, but LESS renal replacement therapy use (25.4% vs 35.3%) — catecholamine-sparing. (c) ADD HYDROCORTISONE (200 mg/day — if vasopressor-dependent): ADRENAL (2018, NEJM) — 90-day mortality no different (27.9% vs 28.8%) BUT faster resolution of shock (median 3 vs 4 days). APROCCHSS (2018, NEJM): hydrocortisone PLUS FLUDROCORTISONE — lower 90-day mortality (43.0% vs 49.1%, P=0.03) and more vasopressor-free days; hyperglycaemia more common (single French network trial — vitamin C was NOT part of the regimen). (d) METHYLENE BLUE (refractory vasoplegia — observational evidence only — see the vasoplegic shock topic): inhibits guanylate cyclase → blocks NO-cGMP pathway → restores vascular tone. (e) ANGIOTENSIN II (refractory vasodilatory shock). (f) TARGET: MAP ≥65 (SEPSISPAM — high 80-85 vs low 65-70: no mortality difference at 28 days (36.6% vs 34.0%) or 90 days; more newly diagnosed atrial fibrillation with the high target; chronic-hypertension subgroup needed less RRT at the high target — 65 is standard). ASSESS PERFUSION: lactate (clearing), urine output, mental status (improving), skin (warm vs mottled)
- SOURCE CONTROL (within 6-12 hours) — (a) IDENTIFY SOURCE: (i) CHEST (pneumonia — CXR, sputum). (ii) ABDOMEN (perforation, abscess, cholangitis, pancreatitis — CT, ultrasound). (iii) URINARY (pyelonephritis, obstructed — ultrasound/CT). (iv) SKIN/SOFT TISSUE (cellulitis, necrotising fasciitis — exam). (v) LINE (central venous catheter — remove if infected). (vi) CSF (meningitis — lumbar puncture if safe). (vii) ENDOCARDITIS (echo, blood cultures). (b) INTERVENE: (i) DRAIN (abscess — percutaneous/surgical; empyema — chest tube; cholangitis — ERCP). (ii) DEBRIDE (necrotising fasciitis — emergency surgery; infected necrosis — step-up approach). (iii) REMOVE DEVICE (infected central line — remove; urinary catheter — change/remove; prosthetic — may need surgery). (iv) REPAIR (perforation — surgery). (c) TIMING: within 6-12 HOURS (SSC 2021 — early source control improves outcomes — delayed worsens). (d) ANTIBIOTICS + source control TOGETHER (don't rely on antibiotics alone — if source persists [undrained abscess], antibiotics won't work)
- ONGOING MONITORING + ORGAN SUPPORT — (a) CONTINUOUS: BP (arterial line — if on vasopressors), HR, SpO2, ECG, urine output (catheterised), temperature, GCS. (b) LABS: lactate (trend — clearing = improving), blood gas (pH, PaO2, PaCO2, base excess), FBC, U&E (renal), LFTs, coagulation, CRP, procalcitonin (guide antibiotic duration). (c) IMAGING: CXR (source + ARDS), CT (source — abdomen, chest — if source not identified). (d) ECHO: cardiac function (septic cardiomyopathy — LV dysfunction + RV dysfunction — need inotrope if cardiac component). (e) ORGAN SUPPORT: ventilation (if ARDS/respiratory failure — lung-protective), RRT (if AKI — AEIOU — CRRT preferred if shocked), transfusion — restrictive threshold (avoid unnecessary transfusion). (f) DAILY REVIEW: antibiotics (de-escalate at 48-72h — PCT-guided — PRORATA: 2.7 more antibiotic-free days by day 28 with non-inferior mortality), vasopressors (wean as shock resolves), fluids (restrict if overloaded — negative balance once stable). (g) AVOID HARM: DVT prophylaxis (LMWH), stress ulcer prophylaxis (if ventilated >48h or coagulopathy), glucose control — moderate targets, avoid hypoglycaemia, normothermia (avoid fever — worsens outcomes), minimise sedation (SAT + SBT). (h) NUTRITION: early enteral (within 48h — maintains gut barrier). (i) GLYCAEMIC CONTROL: moderate targets — avoid hypoglycaemia AND severe hyperglycaemia
- DE-ESCALATION + RECOVERY — (a) ANTIBIOTIC DE-ESCALATION at 48-72h: (i) Based on cultures + sensitivities — narrow to specific organism. (ii) STOP if NO INFECTION (cultures negative + alternative diagnosis). (iii) DURATION: 7 days (standard — but individualise — PCT-guided shortening is supported by PRORATA [2.7 more antibiotic-free days by day 28, non-inferior mortality]; longer for complicated [endocarditis, osteomyelitis, abscess — weeks]). (b) VASOPRESSOR WEANING: (i) As shock resolves (MAP >65 on decreasing dose + lactate normalised + urine improving). (ii) Wean SLOWLY (stepwise reductions — assess tolerance). (iii) Wean vasopressin FIRST (then noradrenaline) OR noradrenaline first (practice varies — some wean the higher dose first). (iv) HYDROCORTISONE: review daily and stop once vasopressors are no longer required — no prolonged taper is mandated (ADRENAL stopped at shock resolution; VANISH tapered over 6 days per its protocol — follow local practice). (c) FLUID MANAGEMENT: (i) Once stable -> achieve NEUTRAL or NEGATIVE balance (mobilise fluid accumulated during resuscitation — diurese [frusemide] if overloaded). (ii) AVOID ongoing positive balance (worsens outcomes). (d) RECOVERY SIGNS: MAP >65 without vasopressors, lactate <2, urine >0.5 mL/kg/hr without diuretics, improving mental status, normothermia. (e) DISCHARGE from ICU: when stable (off vasopressors, adequate urine, improving — no organ support or minimal). (f) POST-SEPSIS: PICS (cognitive impairment, depression, PTSD, weakness — ABCDEF bundle prevents), follow-up clinic, rehabilitation
- PROGNOSIS + GOALS OF CARE — (a) MORTALITY: hospital mortality over 40% (Sepsis-3 — the sickest ICU patients — even with optimal treatment). (b) PREDICTORS of poor outcome: (i) AGE (older — worse). (ii) COMORBIDITY (immunocompromised, cirrhosis, malignancy, CKD — worse). (iii) SOURCE (pneumonia, peritonitis — higher mortality; urinary — lower). (iv) ORGAN FAILURES (more organs = worse — SOFA score). (v) LACTATE (higher + not clearing = worse). (vi) TIMING of treatment (delayed antibiotics/fluids = worse — each hour matters). (vii) FLUID OVERLOAD (excess positive balance = worse — ARDS, abdominal compartment). (c) GOALS OF CARE: (i) If improving -> continue full treatment. (ii) If DETORIORATING (despite maximal support — rising SOFA, worsening lactate, multi-organ failure) -> consider de-escalation or withdrawal (discuss with family — prognosis, quality of life, advance directives). (iii) Palliative care involvement (symptom management + family support — even during active treatment). (d) SURVIVORSHIP: PICS (cognitive, psychological, physical — common after sepsis), prolonged rehabilitation, follow-up. (e) RECURRENCE: depends on source + immunity (if immunocompromised -> recurrent sepsis risk). (f) KEY: septic shock is life-threatening — EARLY treatment (hour-1 bundle) is the most important intervention — but even with optimal care, hospital mortality is over 40% (Sepsis-3)
SAQ — Vasopressor escalation in refractory septic shock
10 minutes · 10 marks
A 65-year-old woman in septic shock from a biliary source has received 30 mL/kg of balanced crystalloid. Her MAP is 60 mmHg on noradrenaline 0.5 mcg/kg/min, with a lactate of 4.0 mmol/L, mottled peripheries, and a central venous saturation of 65%. Outline your vasopressor escalation strategy.
SAQ — Source control and antibiotic de-escalation in septic shock
10 minutes · 10 marks
A 55-year-old man with septic shock from an intra-abdominal source has been on piperacillin-tazobactam and vancomycin for 72 hours. Blood cultures from admission grow Escherichia coli sensitive to all tested agents. He is clinically improving (afebrile, MAP 75 on no vasopressors, lactate 1.5). The team asks whether to continue, narrow, or stop antibiotics.
References20ShowHide
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