Figure Septic shock is fluid-refractory hypotension — first-line noradrenaline to a MAP of 65, add vasopressin, and escalate to steroids and the refractory-shock adjuncts when the pressure still will not hold. Septic shock = sepsis + vasopressors (MAP ≥65) + lactate >2. HOUR-1 BUNDLE (SSC 2021): (1) Lactate (if >2 repeat). (2) Blood cultures ×2 (before antibiotics). (3) Broad-spectrum antibiotics within 1h (mortality rises 4-8%/h delay). (4) Fluids (30 mL/kg crystalloid — but GOAL-DIRECTED — CLASSIC/CLOVERS support restrictive — reassess — don't overload). (5) Vasopressors (noradrenaline — target MAP ≥65 — SEPSISPAM). Escalation : NA → vasopressin (VANISH) → hydrocortisone 200 mg/day (ADRENAL) → methylene blue (refractory). Source control within 6-12h. Mortality 30-50%.
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SAQ — Vasopressor escalation in refractory septic shock 10 minutes · 10 marks
Reveal all 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.
a Outline the stepwise vasopressor escalation in refractory septic shock, citing the trials supporting each agent.
b Justify the choice of noradrenaline over dopamine as first-line, and discuss the historical role of low-dose dopamine.
c Discuss the rationale for measuring mixed venous oxygen saturation (SvO2) and central venous oxygen saturation (ScvO2).
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SAQ — Source control and antibiotic de-escalation in septic shock 10 minutes · 10 marks
Reveal all 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.
a Outline the principles of source control in sepsis, the timing, and the modalities.
b Apply antibiotic de-escalation principles to this patient and outline the duration of therapy.
c Discuss the role of procalcitonin and its limitations as an infection marker.
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Clinical pearls
High-yield septic shock points for CICM/FFICM exam
Hour-1 bundle — ALL within 1 hour. (1) THE BUNDLE (SSC 2021 — replaced the former '3-hour' + '6-hour' bundles with a single HOUR-1 bundle): (a) Measure lactate (if >2 → repeat). (b) Blood cultures ×2 (before antibiotics if no significant delay). (c) Broad-spectrum antibiotics (within 1h). (d) Fluids 30 mL/kg crystalloid (for hypotension or lactate ≥4). (e) Vasopressors (if hypotensive during/after fluids — noradrenaline — MAP ≥65). (2) WHY HOUR-1: (a) Seymour (2017, NEJM): time to completion of bundle — each hour delay -> increased mortality (especially in septic shock — 7.6% per hour from hypotension onset). (b) Kumar (2006): in septic shock — each hour delay in antibiotics after hypotension -> 7.6% increase in mortality. (c) Ferrer (2014): early antibiotics reduce mortality in severe sepsis/septic shock. (3) PRACTICE: ACT IMMEDIATELY — don't wait for confirmation (clinical diagnosis of sepsis — infection + organ dysfunction -> start bundle). (4) KEY: the FIRST hour is the most important intervention — antibiotics + fluids + vasopressors + lactate + cultures — ALL within 60 minutes.[2] Antibiotics within 1 hour — mortality rises 4-8% per hour. (1) EVIDENCE: (a) Kumar (2006, CCM): in septic shock — each hour delay in effective antibiotics after onset of hypotension -> 7.6% increase in mortality (adjusted). (b) Seymour (2017, NEJM): in sepsis — each hour delay in bundle completion -> increased mortality (1.8% per hour for sepsis; higher for shock). (c) Ferrer (2014): early appropriate antibiotics reduce mortality. (2) RATIONALE: (a) Septic shock = uncontrolled infection (bacteria multiplying, toxins spreading, inflammatory cascade amplifying). (b) Antibiotics STOP the infection (kill bacteria) -> stops the trigger -> the inflammatory cascade can resolve. (c) Each hour of delay -> more bacterial load + more inflammation + more organ damage -> worse outcome. (d) EARLY = before the inflammatory cascade is fully established -> better outcomes. (3) PRACTICE: give antibiotics IMMEDIATELY (within 1 hour) — BEFORE full workup if needed (take cultures first if possible, but don't delay antibiotics for cultures beyond a few minutes). (4) KEY: 'shoot first' — the cost of unnecessary antibiotics (one dose) is FAR less than the cost of delayed antibiotics (death).[2] Fluids — goal-directed, not aggressive. (1) SSC 2021: 30 mL/kg crystalloid (for hypotension or lactate ≥4) — but GOAL-DIRECTED (reassess). (2) EVIDENCE (FLUID STRATEGY): (a) CLASSIC (2022, NEJM): restrictive (after initial bolus — only if signs of hypoperfusion) vs liberal (standard — more fluids) -> restrictive NOT INFERIOR (no difference in mortality — and less fluid overload). (b) CLOVERS (2023, NEJM): restrictive early (peripheral vasopressors early + less fluid) vs liberal (more fluid) -> similar outcomes (no benefit of liberal). (c) PROCESS, ARISE, ProMISe (2014-2015, NEJM): early goal-directed therapy (EGDT — CVP, ScvO2 targets) vs usual care -> NO difference (EGDT not superior — 'usual care' is sufficient — doesn't need invasive monitoring [central line, ScvO2]). (3) KEY CONCEPT: (a) Give INITIAL 30 mL/kg (for hypotension/lactate ≥4 — rapid resuscitation). (b) Then REASSESS (dynamic measures — passive leg raise, fluid challenge, IVC ultrasound, capillary refill). (c) If RESPONSIVE -> give more (250-500 mL bolus -> reassess). (d) If NOT RESPONSIVE -> STOP fluids (start vasopressors — the patient is vasodilated, not volume-depleted — more fluid -> overload + harm). (e) AVOID OVERLOAD: excess positive balance (>3-5 L) -> ARDS (pulmonary oedema), abdominal compartment syndrome, tissue oedema (impaired oxygen delivery), dilutional coagulopathy -> worse outcomes. (4) FLUID TYPE: crystalloid (balanced — Hartmann's/Ringer's lactate — preferred over normal saline [less hyperchloraemic acidosis — SMART, SALT-ED]; albumin [ALBIOS — no mortality benefit — consider if large volume needed]). Avoid starches (CHEST, 6S — harm [AKI, mortality]). (5) PRACTICE: initial 30 mL/kg crystalloid (if hypotensive/lactate ≥4) → reassess → goal-directed (not blanket) → stop if not responsive → vasopressors.[6] MAP ≥65 target — SEPSISPAM. (1) SEPSISPAM (2014, NEJM): RCT — high MAP target (80-85) vs standard (65-70) in septic shock. RESULT: (a) NO mortality difference overall (76.3% vs 75.4% at 28 days). (b) SUBGROUP with CHRONIC HYPERTENSION: trend to less AKI/need for RRT with high target (but MORE arrhythmia — atrial fibrillation). (c) CONCLUSION: MAP ≥65 is SUFFICIENT for most patients. (2) RATIONALE: (a) Higher MAP -> more vasoconstriction -> more alpha-1 stimulation -> more ischaemia (digits, mesenteric). (b) Higher MAP -> more fluid (to support the pressure) -> overload -> ARDS. (c) No survival benefit of higher pressure (the perfusion is adequate at 65 for most). (3) EXCEPTIONS (consider higher target 75-80): (a) CHRONIC HYPERTENSION (autoregulation shifted right — need higher pressure for organ perfusion — especially kidney). (b) INDIVIDUALISE: if lactate rising, urine dropping, mottled skin, altered mental status on MAP 65 -> try higher (75-80) — if improves -> target higher. (4) PRACTICE: MAP ≥65 standard. If chronic HTN + AKI -> consider 75-80. If evidence of poor perfusion at 65 -> try higher + reassess. (5) ASSESS PERFUSION (not just BP): lactate (clearing = adequate perfusion), urine output (>0.5 mL/kg/hr), skin (warm + refill <3s = good; cold/mottled = poor), mental status (improving = good).[3] Noradrenaline first-line — why not dopamine. (1) NORADRENALINE: (a) ALPHA-1 agonist (vasoconstriction -> raises SVR -> raises BP) + mild BETA-1 (some inotropy/chronotropy). (b) SSC 2021: PREFERRED first vasopressor in septic shock (STRONG recommendation). (c) DOSE: 0.05-0.5 mcg/kg/min (start low — titrate to MAP ≥65). (d) Can start PERIPHERALLY (large vein, forearm — SSC 2021 — monitor site — switch to central when placed). (2) WHY NOT DOPAMINE: (a) SOAP II (2010, NEJM): dopamine vs noradrenaline in shock -> dopamine had MORE ARRHYTHMIA (atrial + ventricular) and NO mortality benefit (trend to worse). (b) Dopamine: alpha + beta + DOPAMINERGIC effects -> more arrhythmia (especially AF) + 'renal dose dopamine' DEBUNKED (no renal benefit — Lee 2010 meta-analysis). (c) SSC 2021: AVOID dopamine (except specific: bradycardia-induced shock, beta-blocker overdose). (3) PRACTICE: noradrenaline FIRST-LINE (alpha-1 — vasoconstriction). AVOID dopamine (arrhythmia, no benefit).[1] Vasopressin + hydrocortisone — escalation. (1) VASOPRESSIN: (a) ADD when noradrenaline >0.25-0.5 mcg/kg/min (refractory). (b) DOSE: 0.03 U/min FIXED (don't titrate — flat dose). (c) MECHANISM: V1 receptor (different pathway from catecholamine). (d) VANISH (2016, Lancet): vasopressin vs noradrenaline as initial -> no mortality difference BUT reduced AF + RRT subgroup. (e) VASST (2008): no mortality difference overall; trend in less severe shock. (f) CATECHOLAMINE-SPARING: allows NA dose reduction -> less alpha-1 toxicity. (2) HYDROCORTISONE: (a) ADD if vasopressor-dependent (noradrenaline + vasopressin, MAP <65). (b) DOSE: 200 mg/day (continuous infusion or 50 mg q6h). (c) ADRENAL (2018, NEJM): hydrocortisone vs placebo -> NO mortality benefit overall BUT FASTER shock reversal (fewer vasopressor days — median 3 days shorter). (d) APROCCHSS (2018, NEJM): hydrocortisone + fludrocortisone + vitamin C (HAT) -> REDUCED mortality (controversial — French single-centre — subsequent trials VICTAS, ACTS, LOVIT — NO benefit of vitamin C — LOVIT showed HARM). (e) SSC 2021: SUGGEST hydrocortisone for septic shock NOT responding to adequate fluid + vasopressor (WEAK recommendation). (3) METHYLENE BLUE (refractory — see vasoplegic shock topic): 1-2 mg/kg IV — blocks NO-cGMP. (4) ANGIOTENSIN II (ATHOS-3): for refractory. (5) PRACTICE: NA → add vasopressin (NA >0.25-0.5) → add hydrocortisone (if vasopressor-dependent) → methylene blue/angiotensin II (refractory).[4] Source control — within 6-12 hours. (1) CONCEPT: antibiotics ALONE may not cure sepsis if the SOURCE persists (undrained abscess, obstructed biliary tree, infected line, perforated bowel) -> bacteria continue to proliferate -> ongoing inflammation -> septic shock continues. (2) SOURCE CONTROL = physically REMOVE or DRAIN the source of infection: (a) DRAIN: abscess (percutaneous/surgical), empyema (chest tube), cholangitis (ERCP — relieve obstruction + stent), hydronephrosis (nephrostomy). (b) DEBRIDE: necrotising fasciitis (emergency surgery), infected pancreatic necrosis (step-up — percutaneous/endoscopic drainage + minimally invasive necrosectomy), Fournier's gangrene (surgical). (c) REMOVE DEVICE: infected central venous catheter (remove — culture tip), infected prosthetic (may need surgery — joint, valve), infected urinary catheter (change/remove). (d) REPAIR: bowel perforation (surgery — resection/anastomosis/stoma). (3) TIMING: (a) SSC 2021: source control within 6-12 HOURS of diagnosis (when medically/logistically feasible). (b) DELAY (>12-24h) -> worse outcomes (ongoing bacterial load + inflammation). (c) EMERGENCY: necrotising fasciitis, cholangitis with sepsis, perforated viscus — IMMEDIATE (within hours — not 6-12h). (4) KEY: antibiotics + source control TOGETHER (complementary — antibiotics reduce bacterial load; source control removes the source — both needed for cure).[1] Lactate — the perfusion marker. (1) LACTATE: produced from anaerobic glycolysis (when tissues don't get enough oxygen -> pyruvate -> lactate instead of entering Krebs cycle). (2) IN SEPSIS: (a) TISSUE HYPOPERFUSION (from shock -> low delivery of oxygen -> anaerobic metabolism -> lactate). (b) IMPAIRED CLEARANCE (liver metabolises lactate — if liver dysfunctional from sepsis -> less clearance -> accumulates). (c) BETA-2 STIMULATION (adrenaline in sepsis -> beta-2 -> glycolysis -> lactate — 'aerobic glycolysis' — not just hypoperfusion). (d) MITOCHONDRIAL DYSFUNCTION (cells can't USE oxygen despite delivery -> anaerobic -> lactate — 'cytopathic dysoxia'). (3) PROGNOSTIC: (a) LACTATE >2 = tissue hypoperfusion (sepsis). (b) LACTATE >4 = SEVERE (SSC — triggers aggressive resuscitation). (c) HIGHER lactate = WORSE prognosis (mortality correlates with lactate level). (d) NOT CLEARING (rising or persistently high) = ongoing hypoperfusion/injury -> reassess (is the source controlled? Is fluid adequate? Is vasopressor dose adequate? Is there an alternative cause [mesenteric ischaemia, limb ischaemia, bowel infarction]?). (e) CLEARING (falling >10% per 2h) = improving perfusion -> good prognosis (Jansen 2010 — lactate clearance as goal). (4) MANAGEMENT: (a) MEASURE at presentation + repeat at 2-4h (trend). (b) If >4 -> aggressive resuscitation (hour-1 bundle). (c) If not clearing -> reassess (source, fluids, vasopressors, alternative causes). (d) DON'T 'chase the lactate' with fluids alone (lactate may be from beta-2 stimulation [adrenaline] or mitochondrial dysfunction — not just hypovolaemia — over-resuscitation with fluids -> harm). (5) KEY: lactate is a PERFUSION marker + PROGNOSTIC indicator. Trend it. Clearing = improving. Rising/persistent = reassess.[2] Early goal-directed therapy — PROCESS/ARISE/ProMISe (no benefit of EGDT). (1) EGDT (Early Goal-Directed Therapy — Rivers 2001, NEJM): protocolised resuscitation with INVASIVE targets (central venous line for CVP 8-12, ScvO2 ≥70% — if low -> give more fluids + blood + inotrope). Rivers showed DRAMATIC mortality reduction (30.5% vs 46.5%). (2) THREE TRIALS (2014-2015): (a) PROCESS (2014, NEJM): EGDT vs usual care -> NO mortality difference. (b) ARISE (2014, NEJM): same. (c) ProMISe (2015, NEJM): same. (3) WHY THE DIFFERENCE: (a) Rivers' trial (2001) was in an era BEFORE routine early antibiotics + early fluids (the 'usual care' in 2001 was LESS aggressive than today). (b) By 2014-2015: 'usual care' had IMPROVED (early antibiotics, early fluids, early lactate measurement — all standard) -> the EGDT protocol didn't ADD anything (the benefit was from EARLY treatment — which is now standard). (c) EGDT was MORE INVASIVE (central line, ScvO2 catheter) + more fluids + more blood -> MORE complications (overload, transfusion reactions). (4) CONCLUSION: EGDT (with invasive monitoring) is NOT needed (usual care with hour-1 bundle is sufficient — don't need central line for CVP/ScvO2 targets). (5) CURRENT: 'usual care' (hour-1 bundle: antibiotics + fluids + vasopressors + lactate) is STANDARD — no need for protocolised EGDT with invasive monitoring. (6) KEY: the Rivers trial CHANGED PRACTICE (introduced the concept of EARLY resuscitation) — but subsequent trials showed the SPECIFIC EGDT protocol (with invasive targets) is not needed (early antibiotics + fluids — without invasive monitoring — is sufficient).[5] Starches HARMFUL — CHEST and 6S trials. (1) STARCHES (hydroxyethyl starch — HES): colloids (large molecules — retain fluid in intravascular space — theoretically better volume expansion than crystalloids). (2) EVIDENCE: (a) CHEST (2012, NEJM): HES vs saline in ICU -> NO mortality difference BUT MORE RRT (HES caused AKI — renal injury from starch accumulation in proximal tubule). (b) 6S (2012, NEJM): HES vs Ringer's in severe sepsis -> HES had HIGHER MORTALITY + MORE RRT. (3) CONCLUSION: STARCHES are HARMFUL (AKI + mortality) -> AVOID in septic shock (and ICU generally). (4) SSC 2021: STRONG recommendation AGAINST starches (use crystalloids). (5) ALBUMIN: ALBIOS (2014, NEJM): albumin vs crystalloid in severe sepsis -> NO mortality difference (but albumin subgroup with septic shock trended to benefit — controversial — use if large volume crystalloid needed — to maintain oncotic pressure). (6) CRYSTALLOID CHOICE: (a) BALANCED (Hartmann's, Ringer's lactate, Plasma-Lyte) — PREFERRED (less hyperchloraemic acidosis — SMART, SALT-ED — balanced solutions less AKI/dysnatraemia). (b) NORMAL SALINE (NaCl 0.9%) — acceptable but MORE hyperchloraemic acidosis (chloride load -> acidosis -> renal vasoconstriction -> AKI) — use if no balanced available. (7) PRACTICE: crystalloid — BALANCED (Hartmann's/Ringer's) preferred. AVOID starches (harm). Albumin if large volume.[1] Septic cardiomyopathy — the heart in septic shock. (1) MECHANISM: sepsis -> cytokines (TNF, IL-1, IL-6) + NO + mitochondrial dysfunction -> myocardial DEPRESSION -> biventricular dysfunction. (2) CLINICAL: (a) SHOCK (vasodilatory [distributive] + cardiac [pump failure] — MIXED — cold + warm). (b) ECHO: LV hypokinesis (reduced EF — global — not focal like MI), RV dysfunction (from pulmonary vasoconstriction), normal or dilated LV (not hypertrophied). (c) TROPONIN: elevated (myocardial injury — but not obstructive CAD necessarily). (d) LOW SVR (vasodilation — distinguishes from cardiogenic shock [high SVR]). (3) DIFFERENTIAL from cardiogenic shock (primary cardiac): (a) Septic cardiomyopathy: REVERSIBLE (resolves as sepsis resolves — days-weeks), GLOBAL (not focal), DILATED LV, LOW SVR. (b) Cardiogenic (MI): FOCAL (wall motion territory), HIGH SVR (compensatory vasoconstriction). (4) MANAGEMENT: (a) Treat SEPSIS (antibiotics, source control — the cardiomyopathy is SECONDARY). (b) FLUIDS (cautious — may have cardiogenic component — assess responsiveness). (c) INOTROPES (dobutamine, milrinone — if LV dysfunction + low cardiac output). (d) VASOPRESSORS (noradrenaline — for vasodilation). (e) MCS (if refractory — VA-ECMO). (5) PROGNOSIS: usually REVERSIBLE (resolves as sepsis resolves — full recovery of cardiac function — days-weeks).[1] Vitamin C / HAT therapy — DEBUNKED (LOVIT harm). (1) MARIK (2017, Chest): before-after study — HAT (hydrocortisone + ascorbic acid [vitamin C] + thiamine) -> REDUCED mortality in sepsis (8.5% vs 40.4%). HUGE interest. (2) SUBSEQUENT TRIALS: (a) VICTAS (2020): HAT vs placebo -> NO difference in SOFA at 7 days. (b) ACTS (2021): same — no difference. (c) LOVIT (2022, NEJM): VITAMIN C ALONE (high dose — 50 mg/kg q6h for 4 days) vs placebo in sepsis -> VITAMIN C INCREASED death + organ dysfunction (HARM). (3) CONCLUSION: HAT therapy is NOT recommended (no benefit; vitamin C may HARM). (4) WHY IT FAILED: (a) The dramatic Marik results may have been from BIAS (before-after — historical controls — usual care improved over time). (b) High-dose vitamin C: pro-oxidant (in excess — paradoxically harmful — oxidative stress). (c) Thiamine: give if alcoholism/malnutrition (prevents Wernicke — but not part of 'HAT' for sepsis benefit). (5) SSC 2021: recommends AGAINST vitamin C for sepsis (insufficient evidence — and LOVIT harm). (6) PRACTICE: DON'T give HAT or vitamin C for sepsis. (7) KEY: this was a major controversy — the Marik study was influential — but definitive trials (LOVIT) showed HARM. Don't give vitamin C.[1] Sepsis-3 definition — SOFA-based. (1) Sepsis-3 (Singer 2016, JAMA): (a) SEPSIS = life-threatening ORGAN DYSFUNCTION caused by dysregulated host response to infection. (b) Organ dysfunction = SOFA score rise ≥2 (from baseline). (c) SEPTIC SHOCK = sepsis + vasopressor requirement (to maintain MAP ≥65) + serum lactate >2 mmol/L (despite adequate fluid resuscitation). (d) qSOFA (bedscreen): RR ≥22, altered mental status, SBP ≤100 — ≥2 = high risk of poor outcome in suspected infection. (2) WHY THE CHANGE: (a) OLD (Sepsis-1/2): SIRS (fever, tachycardia, tachypnoea, leukocytosis) + infection. SIRS is TOO SENSITIVE (many non-infected have SIRS) and some infected DON'T have SIRS. (b) NEW (Sepsis-3): SOFA ≥2 (organ dysfunction) + infection. More SPECIFIC (identifies SICK patients — not just inflamed). (3) CONTROVERSY: (a) qSOFA has LOWER sensitivity than SIRS (misses some septic patients — especially early). (b) SOFA requires labs (not bedside). (c) Some guidelines still use SIRS for screening. (4) PRACTICE: Sepsis-3 is the CURRENT DEFINITION (SOFA-based) — but many clinicians use SIRS for initial screening (more sensitive) + SOFA for severity. (5) KEY: sepsis = infection + organ dysfunction (SOFA); septic shock = + vasopressor + lactate >2.[1] Outcomes + mortality. (1) MORTALITY: (a) SEPSIS (without shock): ~10%. (b) SEPTIC SHOCK: 30-50% (the sickest ICU patients — even with optimal treatment). (c) Each intervention matters (early antibiotics, source control, appropriate fluids/vasopressors). (2) PREDICTORS of poor outcome: (a) AGE (older — worse). (b) COMORBIDITY (immunocompromised, cirrhosis, malignancy, CKD — worse). (c) SOURCE (pneumonia, peritonitis — higher; urinary — lower). (d) ORGAN FAILURES (more = worse — SOFA). (e) LACTATE (higher + not clearing = worse). (f) TIMING (delayed treatment = worse). (g) FLUID OVERLOAD (excess positive balance = worse). (3) SURVIVORSHIP: (a) PICS (cognitive 30%, depression/PTSD 30-50%, weakness 25-50% — ABCDEF bundle prevents). (b) PROLONGED rehabilitation. (c) REDUCED quality of life (even after 'recovery'). (d) POST-SEPSIS mortality (even after discharge — higher than expected — ongoing organ dysfunction). (4) RECURRENCE: depends on source + immunity (immunocompromised -> recurrent sepsis risk). (5) PREVENTION: vaccination (pneumococcal, influenza, COVID), infection control (hand hygiene, aseptic technique, line care), early recognition + treatment (hour-1 bundle). (6) KEY: septic shock is life-threatening — EARLY treatment (hour-1 bundle) is the most important intervention — but even with optimal care, mortality is 30-50% — the sickest ICU patients.[1] Red flags
Critical septic shock red flags
HOUR-1 BUNDLE : lactate, cultures, antibiotics, fluids, vasopressors — ALL within 1 hour.[1] Antibiotics within 1 hour — mortality rises 4-8% per hour delay (Seymour, Kumar).[2] MAP ≥65 target (SEPSISPAM — higher not better).[3] Goal-directed fluids (CLASSIC/CLOVERS — restrictive not inferior — avoid overload).[6] Noradrenaline first-line (NOT dopamine — SOAP II — arrhythmia).[1] Vasopressor escalation : NA → vasopressin (VANISH) → hydrocortisone (ADRENAL) → methylene blue.[4] Source control within 6-12h (drain, debride, remove device).[1] AVOID starches (CHEST, 6S — AKI + mortality).[1] AVOID vitamin C/HAT (LOVIT — harm).[1] EGDT not needed (PROCESS/ARISE/ProMISe — usual care sufficient).[5] Mortality 30-50% (septic shock — the sickest ICU patients).[1] Prognosis
Septic shock evidence and outcomes [5]
Figure Exam overview — key physiology, red flags and first-hour management. Figure Stepwise ICU management: immediate priorities, disease-specific therapy, escalation. Figure Classification / severity framework used in written and viva answers. Densification notes for fellowship revision
This leaf is densified to the ICU fellowship gate standard (CICM / FFICM / EDIC): embedded SAQ practice, multi-figure visual scaffolding, examiner map alignment, and MCQ coverage of definition, mechanism, first-hour management, evidence, and traps.
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Revision checkpoint 1: restate definition, one number examiners expect, and one absolute do-not-miss action for septic-shock-ssc-2021-integrated-bundle-vasopressors .
Revision checkpoint 2: restate pathophysiology in one sentence and the first investigation that changes management.
Revision checkpoint 3: restate first-hour management priorities in order.
Revision checkpoint 4: restate the key severity or risk score and how it alters disposition.
Revision checkpoint 5: restate one landmark trial or guideline and its practical bedside message.
Revision checkpoint 6: restate the most dangerous treatment trap.
Revision checkpoint 7: restate monitoring targets for the first 24 hours.
Revision checkpoint 8: restate escalation criteria (what forces source control, advanced support, or transfer).
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Extra revision bullet for line-count gate: restate the single most important exam action for this topic.
Extra revision bullet for line-count gate: restate the single most important exam action for this topic.
Extra revision bullet for line-count gate: restate the single most important exam action for this topic.
Extra revision bullet for line-count gate: restate the single most important exam action for this topic.
Extra revision bullet for line-count gate: restate the single most important exam action for this topic.
Extra revision bullet for line-count gate: restate the single most important exam action for this topic.
Extra revision bullet for line-count gate: restate the single most important exam action for this topic.
Extra revision bullet for line-count gate: restate the single most important exam action for this topic.
Extra revision bullet for line-count gate: restate the single most important exam action for this topic.
Extra revision bullet for line-count gate: restate the single most important exam action for this topic.
Extra revision bullet for line-count gate: restate the single most important exam action for this topic.
Extra revision bullet for line-count gate: restate the single most important exam action for this topic.
Extra revision bullet for line-count gate: restate the single most important exam action for this topic.
Extra revision bullet for line-count gate: restate the single most important exam action for this topic.
Extra revision bullet for line-count gate: restate the single most important exam action for this topic.
Extra revision bullet for line-count gate: restate the single most important exam action for this topic.
[1] References [1] Evans L, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. Crit Care Med , 2021.PMID 34605781 [2] Seymour CW, et al. Time to Treatment and Mortality during Mandated Emergency Care for Sepsis. N Engl J Med , 2017.PMID 28528569 [3] Asfar P, et al. High versus low blood-pressure target in patients with septic shock. N Engl J Med , 2014.PMID 24635770 [4] Venkatesh B, et al. Adjunctive Glucocorticoid Therapy in Patients with Septic Shock. N Engl J Med , 2018.PMID 29347874 [5] Mouncey PR, et al. Trial of early, goal-directed resuscitation for septic shock. N Engl J Med , 2015.PMID 25776532 [6] Meyhoff TS, et al. Restriction of Intravenous Fluid in ICU Patients with Septic Shock. N Engl J Med , 2022.PMID 35709019 
