1. Septic Shock (Revised — 2026 SSC Update)

Quick Recap

Infectious Diseases System. This is a REVISED version of the existing "1. Septic Shock" protocol, updated against the 2026 Surviving Sepsis Campaign guidelines (Prescott, Antonelli, Alhazzani et al., March 2026 — published after the original protocol was built). Changes from the prior 2021-based version are marked 🔄 2026 throughout. Cross-reference Sepsis Bundles & Source Control (this system) and Vasopressor & Inotrope Selection & Titration (Cardiovascular System) for expanded detail on those specific topics. Please compare against the existing page and archive/replace — notion-update-page is unreliable for edits of this size, so this was built as a new page per established workflow.

1. Definition (Sepsis-3 Consensus — Unchanged in 2026)

• Sepsis: life-threatening organ dysfunction caused by a dysregulated host response to infection
• Organ dysfunction: acute increase in SOFA score ≥2 points attributable to infection (baseline assumed 0 if no known prior organ dysfunction)
• Septic shock: sepsis with vasopressor requirement to maintain MAP ≥65 mmHg AND lactate >2 mmol/L despite adequate fluid resuscitation, in the absence of hypovolemia
• 🔄 2026 — screening tool reversal: the 2026 guideline now favors SIRS criteria and Modified Early Warning Score (MEWS) over qSOFA for sepsis screening, reflecting evidence of qSOFA's limited sensitivity for early identification. This reverses the qSOFA-forward trend of the last decade. qSOFA (≥2 of RR ≥22/min, altered mentation, SBP ≤100 mmHg) remains a legitimate rapid bedside prognostic flag but should not be relied upon as the primary screening tool going forward.
• 🔄 2026 — prehospital screening: standardized screening tools are now suggested even in the prehospital setting (ambulance/flight transport) to reduce time to recognition before hospital arrival.

Note: ~49 million sepsis cases and ~13 million sepsis-related deaths globally per year (2026 guideline's updated global estimate, larger in scope than prior US-specific figures cited previously); mortality 30–50% in septic shock, rising with age.

2. Pathophysiology (Unchanged)

Dysregulated host response to infection involving simultaneous immune stimulation, immune suppression, hypercoagulation, and hypofibrinolysis. Hypotension results primarily from failure of vascular smooth muscle vasoconstriction (peripheral vasodilation, distributive physiology) rather than primary pump failure or volume loss, though relative/absolute hypovolemia (capillary leak, venodilation, reduced oral intake) commonly coexists. Myocardial depression can also occur ("septic cardiomyopathy") and may complicate the hemodynamic picture, sometimes requiring inotropic support in addition to vasopressors.

3. Immediate Stabilization (ABCDE)

Airway/Breathing:

• Secure airway if altered mentation/respiratory failure
• 🔄 2026 — respiratory support device: HFNC now favored as the initial device for sepsis-associated respiratory failure over NIV, with individualized oxygen targets and consideration of awake proning
• 🔄 2026 — tidal volume: higher tidal volumes (6–8 mL/kg) now suggested in the absence of established lung injury — this is distinct from ARDS lung-protective targets; apply standard lung-protective ventilation once ARDS criteria are met (cross-reference ARDS protocol, Respiratory System)

Circulation — the core of initial management:

• Recognize shock clinically BEFORE hypotension is necessarily present — altered mentation, mottling/delayed capillary refill, tachycardia, tachypnea are early signs
• Fluid resuscitation: the 30 mL/kg bolus remains a weak/conditional recommendation, reflecting genuine uncertainty; use balanced crystalloids, NOT normal saline (SMART trial); guide ongoing fluid therapy with dynamic measures (pulse pressure variation, stroke volume variation, POCUS response to passive leg raise/fluid bolus) rather than a fixed volume target
• 🔄 2026 — POCUS-guided resuscitation: newly and explicitly endorsed as a conditional recommendation to guide the resuscitation process itself, not just to confirm shock type
• 🔄 2026 — de-resuscitation: new recommendation to consider active fluid removal after completion of the initial resuscitation phase, to prevent fluid overload — a genuine shift from a purely "resuscitate and hold" mindset toward an explicit two-phase resuscitate-then-de-resuscitate model
• Perfusion target: capillary refill time used in addition to lactate to guide resuscitation (ANDROMEDA-SHOCK-informed; unchanged in 2026)
• Vasopressors: norepinephrine first-line (cross-reference Vasopressor & Inotrope Selection & Titration protocol for full agent selection, titration, and MAP-target discussion, including the individualized-lower-target-in-elderly point reinforced in 2026)
• 🔄 2026 — blood cultures: explicitly reinforced that blood cultures should be drawn before antimicrobial administration wherever this does not meaningfully delay treatment
• 🔄 2026 — prehospital antibiotics: newly suggested for septic shock patients when delays to hospital treatment are expected, feasibility permitting
• Corticosteroids (hydrocortisone 50 mg IV q6h ± fludrocortisone 50 mcg daily): reserve for vasopressor-dependent septic shock despite adequate fluid resuscitation

Disability: treat altered mentation as sepsis-associated encephalopathy pending exclusion of other causes; glucose control (target ~140–180 mg/dL, avoid tight control <110 given hypoglycemia risk).

Exposure:

• Full skin exam for infection source (cellulitis, necrotizing fasciitis, device sites)
• 🔄 2026 — antipyretics: new recommendation against routine antipyretics for improving clinical outcomes (may still be used for symptom relief/comfort) — temperature management should not be treated as a therapeutic target in itself

Checklist:

4. Focused History (Unchanged)

Suspected infection source (respiratory, urinary, abdominal, skin/soft tissue, line-associated, CNS), immunosuppression, recent surgery/procedures, indwelling devices/catheters, recent antibiotics (resistance risk), comorbidities affecting fluid tolerance (heart failure, ESRD), travel/exposure history, prior MDRO colonization.

5. Examination + POCUS (Unchanged, Reinforced)

Focused exam for infection source; skin for rash/necrotizing changes; signs of hypoperfusion (mottling, delayed cap refill, cool extremities in cold shock; warm, bounding pulses in warm/vasodilated shock).

POCUS: cardiac function (assess for septic cardiomyopathy, guide inotrope decision), IVC assessment and passive-leg-raise response for fluid responsiveness, lung ultrasound (concurrent pneumonia source or evolving ARDS), source-focused scanning (free fluid, abscess, biliary/renal pathology) as clinically indicated. 🔄 2026 formally elevates POCUS from a diagnostic adjunct to a conditionally-recommended resuscitation-guiding tool (Section 3).

6. Syndrome Identification (Unchanged)

Distributive shock physiology (low SVR, variable/preserved-to-high cardiac output initially, evolving to mixed picture with septic cardiomyopathy in a subset) — confirm against Undifferentiated Shock framework and exclude major competing causes (cardiogenic, hypovolemic, obstructive) via POCUS before committing fully to a septic shock management pathway.

7. Differential Diagnosis (Unchanged)

8. Severity Assessment

SOFA score — defines sepsis (delta ≥2) and tracks organ dysfunction trajectory over time. 🔄 2026: SIRS/MEWS now preferred over qSOFA for initial screening (Section 1); qSOFA retains a role as a rapid prognostic flag but is no longer the recommended primary screening tool. APACHE II/IV for general ICU severity/prognostication. Lactate level and trend as an adjunct perfusion marker (interpret alongside capillary refill, not in isolation).

9. Investigations

• Bedside: lactate, capillary refill assessment, POCUS (cardiac + volume status + source-focused)
• Labs: CBC, renal/hepatic function, coagulation panel, procalcitonin (adjunct, not diagnostic alone), blood glucose
• Microbiology: blood cultures ×2 (from separate sites) BEFORE antibiotics (do not delay antibiotics beyond a brief window if cultures are difficult to obtain); urine culture, sputum/respiratory cultures, wound/source-site cultures as indicated
• 🔄 2026 — rapid diagnostics: use of rapid diagnostic testing should be guided by local epidemiology and antimicrobial stewardship principles, not applied indiscriminately
• Imaging: source-directed (CXR, CT abdomen/pelvis, etc.) once initial resuscitation underway — do not delay antibiotics for imaging, but do not let hemodynamic-focused care delay imaging needed to identify a source requiring intervention

10. Point-of-Care Ultrasound

Central to both initial shock-type confirmation and ongoing fluid-responsiveness assessment. IVC collapsibility/passive leg raise response to guide further fluid administration; cardiac function assessment to detect septic cardiomyopathy and guide inotrope addition; source-focused scanning integrated into the diagnostic workup. 🔄 2026 adds a conditional recommendation for POCUS specifically to guide the resuscitation process, not only to diagnose shock type or identify a source.

11. Evidence-Based Management (Timeline)

First hour:

• Measure lactate
• Obtain blood cultures before antibiotics
• Administer broad-spectrum empiric antibiotics — 🔄 2026: for probable/definite sepsis WITHOUT shock, this is now a "recommend" (upgraded from "suggest" in 2021), ideally within 1 hour, though certainty of evidence remains very low
• Begin balanced crystalloid resuscitation for hypotension/lactate ≥4
• Apply vasopressors if hypotensive during/after fluid resuscitation to maintain MAP ≥65 (cross-reference Vasopressor protocol)
• 🔄 2026: rapidly evaluate for a source requiring physical intervention (abscess, infected device) as part of this first-hour assessment, not deferred (cross-reference Sepsis Bundles & Source Control protocol)

First 6 hours:

• Reassess volume status and perfusion using dynamic/POCUS measures + capillary refill/lactate trend
• Escalate vasopressors as above; add corticosteroids if vasopressor-refractory
• 🔄 2026 — source control target: pursue source control ideally within 6 hours of diagnosis (a more specific numerical target than 2021's "as soon as medically and logistically practical"), while the guideline is explicit this rests on observational evidence only (certainty rated very low)
• 🔄 2026 — ICU admission: suggest ICU admission within 6 hours for patients requiring ICU-level care

Ongoing (24h+):

• De-escalate antibiotics per culture results and clinical response
• 🔄 2026: consider active fluid de-resuscitation once initial resuscitation phase is complete, rather than only targeting a passive negative balance once shock resolves
• Daily reassessment of organ dysfunction (SOFA trend); glycemic control; standard ICU bundle
• 🔄 2026 — against: routine antipyretics for outcome improvement, probiotics, and beta-blockers as sepsis-specific therapies

Antibiotic selection:

• Empiric broad-spectrum coverage tailored to suspected source and local resistance patterns/antibiogram, narrowed once culture data available
• 🔄 2026 — beta-lactam administration: prolonged/continuous infusion of beta-lactams (after an initial loading dose) is now a strong recommendation over intermittent bolus dosing (upgraded from conditional in 2021), reflecting PK/PD evidence for sustained time-above-MIC in critically ill patients

12. Organ Support (Unchanged, with Respiratory Note)

Vasopressors/inotropes per Vasopressor protocol; mechanical ventilation for concurrent respiratory failure/ARDS (🔄 2026: HFNC-first approach and higher-tidal-volume allowance absent lung injury, per Section 3); CRRT for AKI/refractory acidosis or volume overload; blood products per restrictive transfusion thresholds (generally Hb <7 g/dL trigger absent active bleeding/ischemia); early enteral nutrition once hemodynamically stabilizing; glycemic control; DVT/stress ulcer prophylaxis.

13. Disease-Specific Therapy

• Empiric antibiotics: source- and epidemiology-tailored, per institutional antibiogram
• 🔄 2026: beta-lactams as prolonged/continuous infusion after loading dose (strong recommendation)
• Hydrocortisone 50 mg IV q6h ± fludrocortisone 50 mcg daily for vasopressor-refractory shock only
• 🔄 2026 — avoid: routine antipyretics for outcomes, probiotics, beta-blockers

14. Consultation Matrix

15. Monitoring Framework

Continuous hemodynamic monitoring (arterial line for frequent BP/vasopressor titration), serial lactate, POCUS-guided fluid reassessment, daily SOFA trend, source control adequacy reassessment, antibiotic de-escalation review daily. 🔄 2026: track institutional process metrics (time-to-antibiotics, time-to-source-control) as part of formal performance improvement infrastructure (cross-reference Sepsis Bundles & Source Control protocol, Section 16).

16. ICU Bundle Checklist (Daily)

17. Complications (Unchanged)

ARDS, AKI, DIC, ICU-acquired weakness, secondary/opportunistic infection, critical illness-related corticosteroid insufficiency, post-sepsis syndrome (long-term cognitive/functional impairment in survivors). Prevention: timely source control, antibiotic stewardship, lung-protective ventilation if ARDS develops, glycemic control. Rescue: CRRT for refractory AKI, ECMO in extreme refractory cases (rare, individualized).

18. Escalation & De-escalation (Unchanged)

Escalate: rising vasopressor requirement, worsening SOFA, new organ dysfunction → reassess source control adequacy, broaden antibiotics if resistant organism suspected, consider corticosteroids if not already started.

De-escalate: vasopressor-free, lactate normalized, source controlled, antibiotics narrowed → transition toward standard ward-level care; 🔄 2026: actively pursue fluid de-resuscitation during this phase rather than passive balance monitoring alone.

19. ICU Discharge Criteria

Hemodynamically stable off vasopressors, source controlled, antibiotics on a defined narrow-spectrum course, no escalating organ dysfunction, adequate oral/enteral intake or stable nutrition plan. 🔄 2026: counsel patients/families regarding expected post-sepsis morbidity (physical, cognitive, psychological) and document follow-up planning — reflects the 2026 guideline's expanded post-hospital survivorship focus.

20. Documentation & Medicolegal Checklist

21. Key Guidelines

• 🔄 Surviving Sepsis Campaign 2026 (Prescott, Antonelli, Alhazzani et al., jointly published Intensive Care Med and Crit Care Med, March 2026): 129 statements, 46 entirely new, superseding 2021 for the elements marked above. This is now the current primary reference for this protocol.
• Surviving Sepsis Campaign 2021 (Evans et al.): prior version; substantial content carries forward unchanged, but see inline 2026 updates throughout
• ACEP sepsis guidance: notably diverges on rigid fluid bolus volume and lactate-driven resuscitation (unchanged tension, Section 22)
• Sepsis-3 consensus definitions (Singer et al., JAMA 2016) — definitional framework unchanged

22. Landmark Trials

• Rivers et al. (2001): early goal-directed therapy — 16% absolute mortality reduction; foundational but methodologically distinct from later trials (much higher control-arm mortality than subsequent trials)
• ProCESS, ARISE, ProMISe trials: protocolized EGDT showed NO benefit over usual care in more contemporary, less severely ill cohorts
• ANDROMEDA-SHOCK: capillary-refill-guided vs lactate-guided resuscitation — lactate-driven arm trended toward higher 28-day mortality, informing the dual-marker recommendation (unchanged in 2026)
• SMART trial (2018): balanced crystalloids vs normal saline — balanced solutions associated with better renal outcomes
• PHANTASi trial: prehospital antibiotics — no benefit in 28-day/90-day mortality (though only 4% of the cohort had septic shock, limiting extrapolation) — note the tension with the 2026 guideline's new suggestion to consider prehospital antibiotics for septic shock specifically; this remains an area where guideline recommendation strength exceeds the certainty of the underlying RCT evidence
• 🔄 SCREEN trial (stepped-wedge cluster RCT, 60,055 patients, cited in 2026 guideline): electronic alert + staff education + feedback associated with lower 90-day in-hospital mortality in patients with AND without sepsis (aRR 0.85, 95% CI 0.77–0.93) — supports systems-level PI infrastructure
• 🔄 Hour-1 bundle ED implementation RCT (n=872, cited in 2026 guideline): reduced time to antibiotics by 73 minutes; uncertain but favorable-trending mortality signal (aRR 0.81, 95% CI 0.48–1.39)
• VANISH and VASST trials: vasopressin as adjunct to norepinephrine (cross-reference Vasopressor protocol for full detail)
• ATHOS-3: angiotensin II — catecholamine-sparing, no proven mortality benefit (cross-reference Vasopressor protocol)
• Andrews et al. (2017): 6-hour goal-directed protocol in a resource-limited setting showed HIGHER mortality with protocolized care — illustrates that rigid protocols are not universally beneficial across all care settings; the 2026 guideline's explicit inclusion of substantial low/middle-income-country panel representation (38% of panelists) is a direct response to this kind of context-dependency concern

23. Controversies

The evidence base underlying the "Hour-1/3-hour/6-hour bundle" time-to-antibiotic mortality association has been significantly challenged — the Seymour et al. retrospective analysis has been criticized for non-randomized design and effect size driven mainly by the sickest patients, and the only prospective RCT of early antibiotics (PHANTASi) showed no benefit. 🔄 The 2026 guideline itself now explicitly rates the certainty of evidence for its hour-based timing targets (1-hour antibiotics, 6-hour source control) as very low — this is a notable and welcome piece of epistemic honesty built directly into the current guideline, addressing much of the prior controversy by being upfront about the evidentiary limits rather than presenting these as precisely-established cutoffs.

Optimal fluid volume/strategy remains genuinely unsettled (30 mL/kg remains a weak/conditional recommendation; ACEP explicitly recommends against a fixed-volume approach). Lactate-driven vs capillary-refill-driven resuscitation remains debated post-ANDROMEDA-SHOCK, though the dual-marker approach persists into 2026.

🔄 New 2026-era tensions worth tracking: the qSOFA-to-SIRS/MEWS reversal will require retraining clinicians and updating institutional screening tools that were built around qSOFA over the past decade; the new prehospital antibiotic suggestion sits in tension with PHANTASi's null RCT result; the de-resuscitation recommendation does not specify a precise trigger for when "initial resuscitation" is considered complete, leaving this to clinical judgment.

IDSA's historical non-endorsement (later reversed) of earlier SSC guideline iterations reflects genuine, substantive disagreement among major societies about evidence quality over time — worth knowing this history exists rather than presenting SSC guidance as uncontested consensus at any point in its evolution, including the current 2026 version.

24. References

1. Prescott HC, Antonelli M, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock 2026. Intensive Care Med. 2026 Mar 23. doi:10.1007/s00134-026-08361-1.
2. Prescott HC, Antonelli M, Alhazzani W, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2026. Crit Care Med. 2026;54(4):725-812.
3. Evans L, Rhodes A, Alhazzani W, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. Crit Care Med. 2021;49(11):e1063-e1143.
4. Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315(8):801-810.
5. Hernandez G, Ospina-Tascon GA, Damiani LP, et al. ANDROMEDA-SHOCK. JAMA. 2019;321(7):654-664.
6. Semler MW, Self WH, Wanderer JP, et al. Balanced crystalloids versus saline in critically ill adults (SMART). N Engl J Med. 2018;378(9):829-839.
7. Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345(19):1368-1377.
8. Kalil AC, Gilbert DN, Winslow DL, Masur H, Klompas M. IDSA position statement: why IDSA did not endorse the Surviving Sepsis Campaign guidelines. Clin Infect Dis. 2017;66(10):1631-1635.
9. Kurtz BJ, Kollef MH. Sepsis and Septic Shock. Washington Manual of Critical Care, 4th ed, 2025 (Ch. 3) — note: predates 2026 SSC update.
10. [SCREEN trial — stepped-wedge cluster RCT, cited within 2026 SSC guideline]