Surviving Sepsis Campaign 2026 Guidelines

• Strong ("we recommend") = applies to most patients
• Conditional ("we suggest") = better in specific situations; consider patient values
• Best practice statement = no formal evidence rating but high net benefit

• Rec 1. Performance Improvement Programs*

For hospitals and health systems, recommend using a performance improvement program for sepsis, including sepsis screening for acutely ill high-risk patients; standard operating procedures for treatment; and implementation of sepsis quality improvement strategies.

Guideline ratingStrong FORCertainty: Screening: Moderate, Standard Operating Procedures: Very Low, Quality Improvement: Moderate

• Programs may vary by setting and hospital ability to implement

• Rec 2. Implementation Strategies - Code Sepsis*

For hospitals and health systems, suggest using a 'code sepsis' or 'sepsis huddle' protocol over not using such a protocol.

Guideline ratingSuggest FORCertainty: Low

• Code sepsis protocols involve multidisciplinary team huddle at bedside to discuss and expedite diagnosis and treatment following positive screen

• Rec 3. Prehospital Screening*

In acutely ill adults en route to hospital by ambulance or flight, suggest using a standard sepsis screening tool over not using one.

Guideline ratingSuggest FORCertainty: Very Low

• NEWS2 had best prehospital test performance (sensitivity 73.1%); qSOFA had lowest sensitivity (23.1%) prehospitally

• Rec 4. In-Hospital Sepsis Screening*

For acutely ill patients in hospital, recommend using NEWS, NEWS2, MEWS, or SIRS over qSOFA as a single tool to screen for sepsis.

Guideline ratingStrong FORCertainty: Moderate

• No ideal single tool with high sensitivity AND specificity
• qSOFA positive should alert but not be used as sole screen
• NEWS2 highest sensitivity and specificity of compared tools

• Rec 5. Biomarkers - Sepsis Diagnosis*

Sepsis is a clinical diagnosis and should not be ruled in or ruled out using a single biomarker or diagnostic test.

goodpractice

• Rec 6. Novel Host Response Diagnostics*

There is insufficient evidence to make a recommendation regarding use of novel rapid host response diagnostics.

insufficientevidence

• Examples: MDW, IntelliSep, SeptiCyte Rapid, TriVerity, Sepsis ImmunoScore
• None provide positive/negative result; they categorize post-test risk
• Not definitive; use in combination with clinical evaluation

• Rec 7. Blood Cultures*

For adults with possible, probable, or definite sepsis or septic shock, recommend collecting blood cultures as soon as possible and ideally before administration of antimicrobial therapy.

Guideline ratingStrong FORCertainty: Low

• Blood cultures positive in only 10-20% of sepsis patients
• Prior antibiotic use reduces yield (31.4% to 19.4% at 70 min post-antibiotics)
• Should not delay antimicrobial initiation particularly in hypotension
• Single-site may be equivalent to multi-site per 2025 systematic review
• Repeat cultures recommended for S. aureus, S. lugdunensis, Candida bacteremia/fungemia

• Rec 8. Blood Lactate*

For adults with possible, probable, or definite sepsis or septic shock, suggest measuring blood lactate.

Guideline ratingSuggest FORCertainty: Low

• Fluid administration should be individualized after initial bolus and lactate monitoring rather than continuing until normalization

• Rec 9. Emergency Treatment*

Sepsis and septic shock are medical emergencies; treatment and resuscitation should begin immediately.

goodpractice

• Rec 10. Initial Fluid Resuscitation Volume*

For adults with sepsis-induced hypoperfusion or septic shock, suggest administering at least 30 mL/kg of IV crystalloid in the first 3 hours.

Guideline ratingSuggest FORCertainty: Low

• Consider individual patient characteristics when selecting initial fluid volume
• Perform frequent, ongoing reassessment to avoid under- or over-resuscitation
• Use adjusted or ideal body weight for BMI > 30 kg/m2 (see Table 4)
• Lactate > 2 mmol/L (intermediate) may also benefit from fluid resuscitation
• Fluid-related harms generally occur with far larger volumes (> 50 mL/kg)

• Rec 11. Vasopressor Timing*

For adults with sepsis-induced hypotension, suggest initial IV crystalloid fluid bolus resuscitation followed by vasopressor support if hypotension persists.

Guideline ratingSuggest FORCertainty: Very Low

• In patients with unstable septic shock, immediate concurrent vasopressors with IV fluid may be warranted on case-by-case basis
• Unstable shock: severely reduced BP, mottled skin, ashen appearance, cyanosis/decreased O2 sat, tachycardia, altered mentation

• Rec 12. Peripheral Vasopressor Administration*

In adults with septic shock, suggest starting vasopressors peripherally to restore MAP rather than delaying initiation until central venous access is secured.

Guideline ratingSuggest FORCertainty: Very Low

• Insufficient data to recommend duration, dose, or access route size
• Midline catheters not considered
• 86.6% of panelists use peripheral vasopressors on at least some occasions
• Pooled complication rate for peripheral vasopressor administration: 5.97%
• Requires safety protocol: high-quality peripheral IV, frequent monitoring for extravasation

• Rec 13. MAP Target*

For adults with septic shock, recommend an initial MAP target of 65 mmHg over higher MAP targets.

Guideline ratingStrong FORCertainty: Moderate

• Not feasible to maintain MAP at exactly 65 mmHg; reasonable range (within 5 mmHg) should be used
• Vasopressors should be titrated to maintain MAP within this range

• Rec 14. MAP Target Elderly*

For adults with septic shock aged 65 years or older, suggest an initial MAP range of 60-65 mmHg over higher ranges.

Guideline ratingSuggest FORCertainty: Low

• Meta-analysis showed lower MAP target associated with reduced mortality at longest follow-up in patients ≥65 (RR 0.89, 95% CI 0.81-0.98, high certainty)

• Rec 15. ICU Admission Timing*

For adults with sepsis or septic shock who require ICU admission, suggest admitting patients to the ICU within 6 hours.

Guideline ratingSuggest FORCertainty: Low

• Rec 16. Antibiotic Timing - Septic Shock*

For adults with possible, probable, or definite septic shock, recommend administering antimicrobial therapy immediately, ideally within 1 hour of recognition.

Guideline ratingStrong FORCertainty: Very Low

• Rec 17. Antibiotic Timing - Probable/Definite Sepsis without Shock*

For adults with probable or definite sepsis without shock, recommend administering antimicrobial therapy immediately, ideally within 1 hour of recognition.

Guideline ratingStrong FORCertainty: Very Low

• Rec 18. Antibiotic Timing - Possible Sepsis without Shock*

For adults with possible sepsis without shock, suggest a time-limited course of rapid investigation and if concern for infection persists, administration of antimicrobial therapy within 3 hours from the time when sepsis was first suspected.

Guideline ratingSuggest FORCertainty: Very Low

• Rapid assessment includes history, clinical examination, and diagnostic testing to determine if bacterial infection is most likely etiology

• Rec 19. Assess Infectious vs Non-Infectious Causes*

Clinicians should perform a rapid assessment of the likelihood of infectious vs. noninfectious causes of acute illness in adults with possible sepsis without shock.

goodpractice

• Rec 20. Deferred Antibiotics - Low Infection Likelihood*

For adults with a low likelihood of infection and without shock, suggest deferring antimicrobial therapy while continuing to closely monitor the patient.

Guideline ratingSuggest FORCertainty: Very Low

• Rec 21. Prehospital Antibiotics*

For adults with definite or probable sepsis and hypotension (septic shock) with anticipated time to in-hospital medical evaluation of over 60 min, suggest administering antimicrobial therapy in ambulance or flight.

Guideline ratingSuggest FORCertainty: Very Low

• Prehospital antibiotic delivery should be implemented only after structured process in place to screen for sepsis in ambulance/flight

• Rec 22. Procalcitonin-Guided Initiation*

For adults with possible or probable sepsis or septic shock, suggest using clinical evaluation alone over procalcitonin plus clinical evaluation to decide whether to start antimicrobial therapy.

Guideline ratingSuggest FORCertainty: Very Low

• Rec 23. Source Control - Evaluation*

Adults with sepsis or septic shock should be rapidly evaluated for specific anatomical diagnoses or sources of infection that require emergent source control.

goodpractice

• Rec 24. Source Control - Timing*

For adults with sepsis or septic shock and a specific anatomical diagnosis or source requiring source control, suggest early source control over late, ideally within 6 hours of diagnosis.

Guideline ratingSuggest FORCertainty: Very Low

• Source control: draining abscess, debriding infected necrotic tissue, removing infected device, relieving anatomical blockage
• Common surgical foci: intra-abdominal abscesses, GI perforation peritonitis, cholangitis, cholecystitis, pelvic abscesses, pyelonephritis with obstruction, necrotizing soft-tissue infection, empyema, septic arthritis, infected devices/central catheters
• Earlier source control considered better when feasible
• Prolonged medical stabilization without source control in severely ill patients unlikely to succeed

• Rec 25. Empiric MDR Coverage - High Risk*

For adults with sepsis or septic shock at high risk of infection with a specific MDR pathogen, suggest using empirical antimicrobial therapy with coverage for this MDR pathogen.

Guideline ratingSuggest FORCertainty: Very Low

• Risk factors: colonization with MDR pathogen in prior year, prior MDR infection, prolonged broad-spectrum antibiotics, prolonged hospitalization in high-MDR-prevalence unit
• MDR pathogens: A. baumannii, ESBL-producing GNR, CRE, VRE, MDR Pseudomonas, MRSA

• Rec 26. Empiric MDR Coverage - Low Risk*

For adults with sepsis or septic shock at low risk of infection with a specific MDR pathogen, suggest against using empirical antimicrobial therapy with coverage for this MDR pathogen.

Guideline ratingSuggest AGAINSTCertainty: Very Low

• Rec 27. Empiric Antifungal Coverage*

For adults with sepsis or septic shock, suggest against using empirical antifungal therapy.

Guideline ratingSuggest AGAINSTCertainty: Low

• Consider on case-by-case basis in patients with risk factors: immunosuppression, prolonged antibiotics, prolonged hospitalization, intra-abdominal source of infection

• Rec 28. Empiric Anaerobic Coverage - Low Risk*

For adults with sepsis or septic shock without risk factors for anaerobic infection, suggest using an empiric antibiotic regimen without anaerobic coverage.

Guideline ratingSuggest FORCertainty: Very Low

• When MDR pathogen coverage requires agents with anaerobic activity (pip-tazo, carbapenems), these are appropriate even without specific anaerobic coverage indication

• Rec 29. Empiric Anaerobic Coverage - High Risk*

For adults with sepsis or septic shock with specific risk factors for anaerobic infection, suggest using an empiric antibiotic regimen that includes anaerobic coverage.

Guideline ratingSuggest FORCertainty: Very Low

• Risk factors: intra-abdominal or deep seated gynecological/obstetric source, necrotizing soft-tissue infection, head and neck infection, CNS abscesses or empyema

• Rec 30. Microbiological Surveillance*

There is insufficient evidence to make a recommendation regarding use of departmental (ICU-wide) microbiological surveillance samples of the upper respiratory tract to guide empirical antimicrobial therapy.

insufficientevidence

• In our practice: 36% use departmental surveillance, 64% do not

• Rec 31. Pathogen-Specific Rapid Diagnostics*

For adults with sepsis or septic shock, suggest using pathogen-specific rapid diagnostic tests on a case-by-case basis in selected patients based on clinical features, local pathogen/resistance patterns, seasonality, and availability.

Guideline ratingSuggest FORCertainty: Low

• Mortality benefits when rapid diagnostics are paired with effective antimicrobial stewardship programs

• Rec 32. Candida Biomarkers - Initiation*

For adults with sepsis or septic shock, suggest against using Candida fungal biomarkers to guide initiation of empiric antifungal therapy.

Guideline ratingSuggest AGAINSTCertainty: Low

• May be considered case-by-case in selected high-risk patients (immunosuppression, prolonged antibiotics, prolonged hospitalization, intra-abdominal source)

• Rec 33. Prolonged Beta-Lactam Infusion*

For adults with sepsis or septic shock, recommend using prolonged infusion of beta-lactams for maintenance (after initial loading dose) over bolus administration.

Guideline ratingStrong FORCertainty: Moderate

• Meta-analysis of 18 RCTs (9,108 patients) showed prolonged infusion reduces short-term mortality (RR 0.91; 25 fewer deaths per 1,000 patients, high certainty)
• BLING III RCT supported this recommendation
• Loading dose before prolonged infusion is crucial
• Requires occupying venous catheter lumen; drug stability and compatibility important
• Particularly relevant for beta-lactams with shorter half-life (pip-tazo, carbapenems)

• Rec 34. Therapeutic Drug Monitoring*

For adults with sepsis or septic shock, suggest using antimicrobial therapeutic drug monitoring (TDM) on a case-by-case basis in selected patients, based on clinical features, local pathogen/resistance patterns, drug class, and availability.

Guideline ratingSuggest FORCertainty: Very Low

• Augmented renal clearance, AKI, hypoalbuminemia, RRT, ECLS affect antimicrobial concentrations

• Rec 35. De-escalation - Alternative Diagnosis*

Clinicians should continuously reevaluate patients, search for alternative diagnoses, and discontinue empiric antimicrobial therapy if an alternative cause of illness is demonstrated or strongly suspected in adults with suspected sepsis or septic shock but unconfirmed infection.

goodpractice

• Rec 36. De-escalation - Confirmed Pathogen*

For adults with sepsis or septic shock, recommend de-escalation of antimicrobial therapy over no de-escalation when a confirmed microbiological diagnosis and susceptibility profile is available.

Guideline ratingStrong FORCertainty: Very Low

• De-escalation = discontinuing unnecessary antimicrobials or narrowing the spectrum

• Rec 37. De-escalation - No Pathogen Identified*

For adults with sepsis or septic shock, suggest de-escalation of antimicrobial therapy over no de-escalation when no pathogens are identified on final culture results.

Guideline ratingSuggest FORCertainty: Very Low

• Decision depends on clinical context; high MDR-prevalence settings with limited laboratory services may warrant caution before de-escalating on negative cultures

• Rec 38. Candida Biomarkers - Discontinuation*

For adults with sepsis or septic shock receiving empiric antifungal therapy, suggest against use of Candida fungal biomarkers to guide discontinuation of empiric antifungal therapy.

Guideline ratingSuggest AGAINSTCertainty: Low

• May be considered in selected high-risk patients (immunosuppression, prolonged antibiotics, prolonged hospitalization, intra-abdominal source)

• Rec 39. Duration of Antibiotics - Shorter*

For adults with an initial diagnosis of sepsis or septic shock and adequate source control, suggest using shorter over longer duration of antimicrobial therapy.

Guideline ratingSuggest FORCertainty: Very Low

• BALANCE trial: 7 days non-inferior to 14 days for bloodstream infection

• Rec 40. Procalcitonin-Guided Discontinuation*

For adults with initial diagnosis of sepsis or septic shock and adequate source control where optimal duration is unclear, suggest using procalcitonin AND clinical evaluation to decide when to discontinue antimicrobials over clinical evaluation alone.

Guideline ratingSuggest FORCertainty: Low

• ADAPT-Sepsis RCT confirmed PCT can safely reduce antibiotic duration in sepsis

• Rec 41. Selective Decontamination of Digestive Tract (SDD)*

In mechanically ventilated adults with sepsis or septic shock in units with a low prevalence of antimicrobial resistance, suggest using selective decontamination of the digestive tract.

Guideline ratingSuggest FORCertainty: Moderate

• SDD: nonabsorbable topical antimicrobials to oropharynx and upper GI, plus short-term IV broad-spectrum antibiotics
• Meta-analysis of 32 RCTs: probable reduction in short-term mortality (RR 0.91), more days alive out of ICU, possibly less antimicrobial resistance
• SuDDICU trial: 90-day mortality similar but fewer bloodstream infections (4.9% vs 6.9%) and fewer antibiotic-resistant organisms
• Balance desirable vs undesirable effects in high MDR-prevalence settings on case-by-case basis

• Key figure: Figure 3: Quick guide for resuscitation and hemodynamic support in adults with sepsis and septic shock*

• Rec 42. Blood Pressure Monitoring*

For adults with septic shock, suggest using either invasive or noninvasive blood pressure monitoring.

Guideline ratingSuggest FORCertainty: Very Low

• Invasive monitoring advised in patients who: require intermediate-to-high dose vasopressors, escalating vasopressors, or multiple vasopressors; are receiving frequent arterial blood sampling; or have inconsistent noninvasive measurements
• EVERDAC trial (published after finalization): noninvasive strategy noninferior for 28-day mortality (34.3% vs 36.9%)
• In our practice: 62.7% use invasive monitoring in septic shock

• Rec 43. Fluid Type - Crystalloids First Line*

For adults with sepsis or septic shock, recommend using crystalloids as first-line fluid for resuscitation.

Guideline ratingStrong FORCertainty: Moderate

• Rec 44. Fluid Type - Balanced Crystalloids*

For adults with sepsis or septic shock undergoing initial resuscitation, suggest using balanced crystalloids over 0.9% saline.

Guideline ratingSuggest FORCertainty: Moderate

• For patients with sepsis AND traumatic brain injury, suggest 0.9% saline
• SMART, BaSICS, PLUS trials informed this recommendation
• Balanced solutions probably reduce mortality vs saline (OR 0.94) and new RRT (OR 0.86, high certainty)
• Nonproprietary balanced solutions (Ringer's lactate) often similar cost to 0.9% NS

• Rec 45. Fluid Type - Albumin*

For adults with sepsis or septic shock, suggest using crystalloids alone over crystalloids with supplemental albumin for fluid resuscitation.

Guideline ratingSuggest FORCertainty: Moderate

• Supplemental albumin may be appropriate for patients who already received large crystalloid volumes or have cirrhosis
• Supplemental albumin should be avoided in patients with traumatic brain injury
• No effect of albumin on 28-day mortality (RR 1.01, moderate certainty)

• Rec 46. Fluid Type - No Starches*

For adults with sepsis or septic shock, recommend against using starches for resuscitation.

Guideline ratingStrong AGAINSTCertainty: High

• Rec 47. Fluid Type - No Gelatin*

For adults with sepsis and septic shock, suggest against using gelatin for resuscitation.

Guideline ratingSuggest AGAINSTCertainty: Moderate

• Rec 48. Liberal vs. Restrictive Ongoing Resuscitation*

For adults with sepsis or septic shock who have already received fluid resuscitation with 30 mL/kg and have persistent hypoperfusion, suggest using either a liberal or a restrictive fluid resuscitation strategy based on individual patient and health system factors.

Guideline ratingSuggest FORCertainty: Low

• Wide variability in protocols across trials
• Patient factors: current clinical conditions, chronic illness (e. g. heart failure), availability of monitored beds
• CLOVERS, CLASSIC, other trials showed no mortality difference between strategies
• In low-resource settings, potential harms of fluid overload are greater

• Rec 49. Dynamic Measures for Fluid Resuscitation*

For adults with sepsis or septic shock, suggest using dynamic measures to guide fluid resuscitation over physical examination or static measures alone.

Guideline ratingSuggest FORCertainty: Low

• Dynamic measures: passive leg raise, fluid bolus response using SV, SVV, PP, or PPV
• Meta-analysis: dynamic measures likely reduce mortality (RR 0.91) and RRT (RR 0.75)
• CVP and static filling pressures are poor predictors of fluid responsiveness
• Increases of 10-15% in chosen parameter following challenge are reflective of fluid-responsiveness
• POCUS-guided resuscitation probably reduces 28-day mortality (RR 0.88)

• Rec 50. Cardiac Output Monitoring*

For adults with septic shock, there is insufficient evidence to make a recommendation on using minimally invasive or noninvasive cardiac output monitoring in addition to usual care.

insufficientevidence

• SCCM critical care ultrasound guideline includes conditional recommendation for use in septic shock management

• Rec 51. Serial Lactate*

For adults with sepsis and elevated lactate or septic shock, suggest using serial lactate measurements to guide resuscitation.

Guideline ratingSuggest FORCertainty: Low

• Fluid administration individualized after initial bolus and lactate decrement monitoring
• Do NOT continue fluids until lactate normalization is achieved
• Serial measurements and clearance rates (≥10% reduction every 2hr) better than static normalization
• If lactate unavailable, capillary refill time and urine output are alternatives (per expert Delphi)

• Rec 52. Capillary Refill Time*

For adults with sepsis or septic shock, suggest using capillary refill time to guide resuscitation as an adjunct to other measures of perfusion.

Guideline ratingSuggest FORCertainty: Low

• CRT can change quickly (within 10 min) allowing more timely assessment
• Normalize CRT to ≤3 seconds as a target
• ANDROMEDA-SHOCK-2 (published after finalization): CRT-guided resuscitation associated with better hierarchical composite outcomes (win ratio 1.16)
• Consider ambient lighting, temperature, skin pigmentation, peripheral vascular disease

• Rec 53. Vasopressors - First Line (Norepinephrine)*

For adults with septic shock, recommend using norepinephrine as the first-line agent over dopamine, epinephrine, or selepressin.

Guideline ratingStrong FORCertainty: Dopamine: High, Epinephrine: Low, Selepressin: Low

• Rec 54. Vasopressors - Against Terlipressin*

For adults with septic shock, suggest against using terlipressin.

Guideline ratingSuggest AGAINSTCertainty: Low

• Rec 55. Vasopressors - Norepinephrine over Vasopressin/Ang II*

For adults with septic shock, suggest using norepinephrine as the first-line agent over vasopressin or angiotensin II.

Guideline ratingSuggest FORCertainty: Vasopressin: Low, Angiotensin II: Very Low

• Vasopressin probably reduces RRT use (RR 0.70, moderate certainty)
• Vasopressin and angiotensin II more expensive and less available than norepinephrine
• In low-resource settings without norepinephrine, epinephrine is acceptable alternative (per expert Delphi)

• Rec 56. Vasopressors - Add Vasopressin*

For adults with septic shock on escalating doses of norepinephrine, suggest adding vasopressin.

Guideline ratingSuggest FORCertainty: Moderate

• Meta-analysis of 9 RCTs: probable reduction in mortality with adding vasopressin (RR 0.89)
• Probably results in less atrial fibrillation vs norepinephrine monotherapy (RR 0.66)
• Possibly more digital ischemia (RR 2.87, low certainty)
• In our practice: 85.1% add vasopressin; initiate at median 0.3 μg/kg/min of norepinephrine

• Rec 57. Vasopressors - Add Epinephrine*

For adults with septic shock and inadequate MAP despite norepinephrine and vasopressin, suggest adding epinephrine.

Guideline ratingSuggest FORCertainty: Very Low

• In settings where vasopressin is not available, epinephrine can be added to norepinephrine alone

• Rec 58. Vasopressors - Cardiac Dysfunction*

For adults with septic shock with concomitant cardiac dysfunction, suggest using either norepinephrine or epinephrine as first-line vasopressor.

Guideline ratingSuggest FORCertainty: Very Low

• Norepinephrine may be preferred in patients with tachyarrhythmia or significant sinus tachycardia
• Epinephrine may be preferred in patients with bradyarrhythmia or significant sinus bradycardia

• Rec 59. Methylene Blue*

For adults with refractory septic shock and escalating vasopressor requirements, there is insufficient evidence to make a recommendation on IV methylene blue.

insufficientevidence

• May improve blood pressure; insufficient evidence that it improves survival
• Likely results in reduction in duration of vasopressors (MD -1 day, moderate certainty)
• In our practice: 69% never/almost never use; 23% sometimes use
• May be only viable second-line option in low-resource settings without vasopressin

• Rec 60. Inotropes - Use in Cardiac Dysfunction*

For adults with septic shock and cardiac dysfunction with persistent hypoperfusion despite adequate fluid status and arterial blood pressure, suggest using inotropes over no inotropes.

Guideline ratingSuggest FORCertainty: Very Low

• Inotropes should be used IN ADDITION to (not instead of) vasopressors

• Rec 61. Inotropes - Dobutamine or Epinephrine*

For adults with septic shock with persistent hypoperfusion and cardiac dysfunction despite adequate fluid resuscitation and arterial blood pressure, suggest adding dobutamine to norepinephrine or using epinephrine alone.

Guideline ratingSuggest FORCertainty: Very Low

• Insufficient data to recommend dobutamine vs milrinone
• In our practice: 71.4% use dobutamine, 12.7% use milrinone, 14.3% use epinephrine

• Rec 62. Inotropes - Against Levosimendan*

For adults with septic shock and cardiac dysfunction with persistent hypoperfusion despite adequate volume status and arterial blood pressure, suggest against using levosimendan.

Guideline ratingSuggest AGAINSTCertainty: Low

• Rec 63. Midodrine*

For adults with septic shock and ongoing requirement for vasopressors, there is insufficient evidence to make a recommendation on use of oral midodrine.

insufficientevidence

• In our practice: 32.8% use midodrine; 86.4% use it after acute phase to facilitate IV vasopressor discontinuation

• Rec 64. Beta-Blockers*

For adults with septic shock, suggest against using beta-blockers as a treatment for septic shock.

Guideline ratingSuggest AGAINSTCertainty: Very Low

• Based on evidence for short-acting IV beta-blockers (esmolol and landiolol)
• Probably associated with reduction in new-onset tachyarrhythmias (RR 0.37, moderate certainty)
• Also probably associated with increased duration of vasopressor use (MD 1.04 d more, moderate certainty)

• Rec 65. Oxygenation Monitoring*

For adults with sepsis, suggest measuring oxygenation by either pulse oximeter (SpO2) or arterial blood gas (SaO2) in conjunction with physical examination and clinical acumen.

Guideline ratingSuggest FORCertainty: Very Low

• ABG is gold standard; includes pH, PaCO2, lactate, bicarbonate
• SpO2/FiO2 may substitute for PaO2/FiO2 but less accurate in shock, darker skin tones, SpO2 <90% or >97%
• New global ARDS definition allows use of SpO2-based measurements
• SpO2/FiO2 <315 (if SpO2 <97%) = ARDS diagnosis alternative in resource-limited settings

• Rec 66. Oxygen Targets*

For adults with sepsis and acute hypoxemic respiratory failure, suggest titrating FiO2 to target either higher, more liberal oxygen levels or lower, conservative oxygen levels depending on patient factors and resource limitations.

Guideline ratingSuggest FORCertainty: Low

• Lower target: approximately 90-93% SpO2
• Higher target: SpO2 ≥96%
• In our practice: panelists target SpO2 between 90% (IQR 90-92%) to 96% (IQR 94-98%)
• Little to no difference in mortality between lower vs higher targets (RR 1.02, low certainty)

• Rec 67. HFNC over Conventional Oxygen*

For adults with sepsis and acute hypoxemic respiratory failure, suggest using high flow nasal cannula (HFNC) therapy over conventional oxygen therapy.

Guideline ratingSuggest FORCertainty: Very Low

• Applies to patients with PaO2/FiO2 <200 or SpO2/FiO2 <235
• HFNC: can achieve FiO2 >0.8-0.9, flow rates up to 60 L/min, reduces anatomic dead space
• Based on 11 RCTs (3,546 patients)

• Rec 68. HFNC over NIPPV*

For adults with sepsis and acute hypoxemic respiratory failure, suggest using HFNC as the initial therapy over noninvasive positive pressure ventilation.

Guideline ratingSuggest FORCertainty: Low

• Based on 7 RCTs (2,465 patients); shorter MV duration with HFNC vs NIPPV

• Rec 69. HFNC over Alternating HFNC/NIPPV*

For adults with sepsis and acute hypoxemic respiratory failure, suggest using HFNC over high flow alternating with non-invasive positive pressure ventilation.

Guideline ratingSuggest FORCertainty: Very Low

• Rec 70. Awake Proning*

For adults with sepsis and acute hypoxemic respiratory failure who are not intubated, suggest a trial of awake proning.

Guideline ratingSuggest FORCertainty: Very Low

• Duration and frequency depend on patient tolerance
• Sedation should NOT be used to promote tolerance of proning in non-intubated patients
• 17 RCTs (3,537 patients); slight reduction in intubation need (RR 0.82, low certainty)
• All trials focused on COVID-19 patients

• Rec 71. Tidal Volume - ARDS (Low Volume)*

For adults with sepsis and ARDS, recommend using a low tidal volume ventilation strategy (6 mL/kg IBW) over a high tidal volume strategy (>10 mL/kg IBW).

Guideline ratingStrong FORCertainty: High

• Rec 72. Tidal Volume - Without ARDS*

For adults with sepsis-associated hypoxemic respiratory failure without ARDS, suggest using a tidal volume of 6-8 mL/kg IBW over a lower (4 to <6 mL/kg IBW) tidal volume.

Guideline ratingSuggest FORCertainty: Low

• Patients should be screened regularly for development of ARDS; ARDS diagnosis often missed or delayed
• ARDS under-recognized in 48.7-52.4% of patients who meet criteria
• Lower tidal volumes (4-6 vs 6-8) may increase delirium risk (RR 1.19, moderate certainty)

• Rec 73. Plateau Pressure Limit*

For adults with sepsis and ARDS, recommend using an upper limited goal for plateau pressure of 30 cmH2O over higher plateau pressures.

Guideline ratingStrong FORCertainty: High

• Rec 74. PEEP - Higher in Moderate-Severe ARDS*

For adults with sepsis and moderate-severe ARDS, suggest using higher PEEP over lower PEEP.

Guideline ratingSuggest FORCertainty: Moderate

• Rec 75. PEEP - No Incremental Titration Strategy*

For adults with sepsis and moderate-severe ARDS, recommend against using an incremental PEEP titration strategy.

Guideline ratingStrong AGAINSTCertainty: Moderate

• Rec 76. Prone Ventilation*

For adults with sepsis and moderate-severe ARDS, suggest using prone ventilation for greater than 12 hours daily.

Guideline ratingSuggest FORCertainty: Moderate

• Rec 77. NMBA - Intermittent Boluses*

For adults with sepsis and moderate-severe ARDS, suggest using intermittent NMBA boluses over continuous NMBA infusion.

Guideline ratingSuggest FORCertainty: Moderate

• Rec 78. VV-ECMO*

For adults with severe ARDS due to sepsis, suggest using veno-venous ECMO when conventional mechanical ventilation fails in experienced centers with infrastructure to support its use.

Guideline ratingSuggest FORCertainty: Low

• Rec 79. IV Corticosteroids*

For adults with septic shock, suggest using IV corticosteroids.

Guideline ratingSuggest FORCertainty: Low

• 45 RCTs (9,543 patients): possibly small reduction in 28-day mortality (RR 0.92, low certainty)
• High certainty: greater shock reversal at 7 days (RR 1.29)
• Increases hyperglycemia (RR 1.19) and hypernatremia (RR 1.64, moderate certainty)
• Dose: 200 mg hydrocortisone equivalent per 24h (no increased benefit above 260 mg/day)
• In our practice: 88.4% use; 90% give 200 mg hydrocortisone-equivalent/24h; 86% as intermittent doses
• 63% never provide concomitant fludrocortisone; 61% stop without taper when clinically improving

• Rec 80. Antipyretics*

For adults with sepsis or septic shock, suggest against the use of antipyretic therapy (pharmacologic or surface cooling) for the purpose of improving clinical outcomes.

Guideline ratingSuggest AGAINSTCertainty: Very Low

• Does NOT apply to: pain control, patient symptom control, neuro critical care patients, or patients after cardiac arrest
• Fever masking may delay recognition of new infection

• Rec 81. IV Vitamin C*

For adults with sepsis or septic shock, suggest against using IV vitamin C.

Guideline ratingSuggest AGAINSTCertainty: Low

• 55 RCTs total; no mortality benefit in low risk-of-bias trials
• LOVIT trial was definitive large trial showing no benefit
• Possible factitious hyperglycemia

• Rec 82. IV Immunoglobulin*

For adults with sepsis or septic shock, suggest against using IV immunoglobulins.

Guideline ratingSuggest AGAINSTCertainty: Low

• Rec 83. Blood Purification*

For adults with sepsis or septic shock, suggest against using blood purification techniques, including hemoperfusion, high-dose hemofiltration, or plasma exchange.

Guideline ratingSuggest AGAINSTCertainty: Very Low

• Ongoing TIGRIS RCT (NCT03901807) evaluating polymyxin B hemoperfusion in specific subpopulation with endotoxin 0.60-0.89 and multi-organ failure

• Rec 84. Polymyxin B Hemoperfusion*

For adults with sepsis or septic shock, suggest against using polymyxin B hemoperfusion.

Guideline ratingSuggest AGAINSTCertainty: Low

• Rec 85. Vitamin D*

For adults with sepsis and septic shock, suggest against using Vitamin D therapy for sepsis treatment.

Guideline ratingSuggest AGAINSTCertainty: Very Low

• Does NOT apply to patients on lower-dose Vitamin D for other indications or standard nutritional practice
• VIOLET trial subgroup showed possible harm with high-dose (540,000 IU) enteral vitamin D in sepsis

• Rec 86. XueBiJing*

For adults with sepsis or septic shock, suggest against using XueBiJing injection outside of jurisdictions where it has regulatory approval.

Guideline ratingSuggest AGAINSTCertainty: Very Low

• Rec 87. Stress Ulcer Prophylaxis*

For adults with sepsis or septic shock who have risk factors for GI bleeding, suggest using stress ulcer prophylaxis with proton-pump inhibitors over not using stress ulcer prophylaxis.

Guideline ratingSuggest FORCertainty: Moderate

• PPIs reduced risk of clinically important GI bleeding (RR 0.48, moderate certainty)
• Risk factors: AKI, male gender, coagulopathy, shock, chronic liver failure
• H2-receptor antagonists are reasonable alternative when PPIs unavailable
• Future research: need for SUP in enterally fed patients without other risk factors

• Rec 88. Probiotics*

For adults with sepsis or septic shock, suggest against using probiotics.

Guideline ratingSuggest AGAINSTCertainty: Very Low

• PROSPECT trial (large RCT) showed no benefit on VAP in general ICU population

• Rec 89. Active Fluid Removal*

For adults with septic shock after the acute resuscitation phase, suggest using active fluid removal.

Guideline ratingSuggest FORCertainty: Very Low

• Acute resuscitation refers to: escalating vasopressor doses, ongoing high doses of vasopressors, or needing ongoing volume expansion
• Active fluid removal: diuretics; if insufficient, ultrafiltration or extracorporeal fluid removal
• Factors: cardiorespiratory function; vasopressor dose; clinical course; peripheral edema; weight; fluid balance
• Diuretics-only approach appears more favorable than diuretics+RRT for mortality (RR 0.89 vs 1.13)

• Rec 90. Blood Transfusion*

For adults with sepsis or septic shock, recommend using a restrictive transfusion strategy over a liberal transfusion strategy.

Guideline ratingStrong FORCertainty: Moderate

• Rec 91. Enteral Nutrition*

For adults with sepsis or septic shock, suggest early (within 72 hours) initiation of enteral nutrition.

Guideline ratingSuggest FORCertainty: Very Low

• Rec 92. Insulin Therapy*

For adults with sepsis or septic shock, recommend initiating insulin therapy at a glucose level of ≥180 mg/dL (10 mmol/L).

Guideline ratingStrong FORCertainty: Moderate

• Rec 93. Renal Replacement - Against Without Indication*

For adults with sepsis or septic shock and AKI, with no definitive indication for RRT, suggest against using renal replacement therapy.

Guideline ratingSuggest AGAINSTCertainty: Moderate

• Rec 94. Renal Replacement - CRRT vs IHD*

For adults with sepsis or septic shock and AKI warranting RRT, suggest either continuous or intermittent renal replacement therapy.

Guideline ratingSuggest FORCertainty: Low

• Rec 95. Sodium Bicarbonate - Against (Lactic Acidemia)*

For adults with septic shock and hypoperfusion-induced lactic acidemia, suggest against using sodium bicarbonate therapy to improve hemodynamics or to reduce vasopressor requirements.

Guideline ratingSuggest AGAINSTCertainty: Low

• Rec 96. Sodium Bicarbonate - With Severe Acidemia and AKI*

For adults with septic shock, severe metabolic acidemia (pH ≤7.2), and AKI (AKIN score 2 or 3), suggest using sodium bicarbonate therapy.

Guideline ratingSuggest FORCertainty: Very Low

• Rec 97. VTE Prophylaxis - Pharmacological*

For adults with sepsis or septic shock, recommend using pharmacologic VTE prophylaxis unless a contraindication exists.

Guideline ratingStrong FORCertainty: Moderate

• Rec 98. VTE Prophylaxis - LMWH over UFH*

For adults with sepsis or septic shock, recommend using low molecular weight heparin over unfractionated heparin for VTE prophylaxis.

Guideline ratingStrong FORCertainty: Moderate

• Rec 99. VTE Prophylaxis - Pharmacological Alone*

For adults with sepsis or septic shock, suggest using pharmacological VTE prophylaxis alone over pharmacological VTE prophylaxis plus mechanical VTE prophylaxis.

Guideline ratingSuggest FORCertainty: Moderate

• Rec 100. Goals of Care Discussions*

For adults with sepsis or septic shock, clinicians should discuss goals of care and prognosis with patients and/or families.

goodpractice

• Rec 101. Goals of Care - Timing*

For adults with sepsis or septic shock, suggest addressing goals of care early (within 72 hours) over late (72 hours or later).

Guideline ratingSuggest FORCertainty: Low

• Rec 102. Standardized Criteria for GOC Triggers*

Insufficient evidence to issue a recommendation regarding use of a specific standardized criterion to identify patients for goals of care discussions.

insufficientevidence

• Rec 103. Advanced Directives - Discharge*

Health systems should implement strategies to ensure that patients being discharged from hospital after sepsis or septic shock have the opportunity to execute advanced directives.

goodpractice

• Rec 105. Time-Limited Trials*

Insufficient evidence to issue a recommendation regarding formal time-limited trials (TLTs) of critical care.

insufficientevidence

• TLT: collaborative plan to use life-sustaining therapy for defined duration; response to therapy informs decision to continue/escalate or transition to comfort
• In our practice: 64% use TLTs

• Rec 106. Palliative Care*

The principles of palliative care should be integrated into the treatment plan, when appropriate, to address patient and family symptoms and suffering.

goodpractice

• Rec 107. Routine Palliative Care Consultation*

For adults with sepsis or septic shock, suggest against routine formal palliative care consultation for all patients over palliative care consultation based on clinician judgment.

Guideline ratingSuggest AGAINSTCertainty: Low

• Rec 108. ICU-to-Floor Transition Program*

For adults with sepsis and septic shock admitted to ICU, suggest using a critical care transition program compared with usual care, upon transfer to the floor.

Guideline ratingSuggest FORCertainty: Very Low

• Rec 109. Handoff Process*

For adults with sepsis or septic shock, suggest using a handoff process of critically important information at transitions of care.

Guideline ratingSuggest FORCertainty: Very Low

• Rec 112. Medication Reconciliation - Pharmacist*

For adults with sepsis or septic shock, suggest comprehensive medication reconciliation using a pharmacist-based approach at transitions in care.

Guideline ratingSuggest FORCertainty: Very Low

• May reduce prescription of atypical antipsychotics and PPIs beyond need

• Rec 124. Post-Hospital Follow-Up*

Health systems should facilitate assessment and follow-up for physical, cognitive, and emotional problems after hospital discharge for sepsis or septic shock.

goodpractice

• Rec 125. Post-Critical Illness Follow-Up Services*

For adult survivors of hospitalization for sepsis or septic shock, suggest offering post critical illness follow-up services.

Guideline ratingSuggest FORCertainty: Low

• Probable small improvements in quality of life physical health, anxiety, PTSD

• Rec 126. Physical Rehabilitation*

For adult survivors of hospitalization for sepsis or septic shock who received invasive mechanical ventilation >48 hours, suggest offering physical rehabilitation services after hospital discharge.

Guideline ratingSuggest FORCertainty: Low

• Rec 127. Mental Health Services*

For adult survivors of hospitalization for sepsis or septic shock, suggest offering services that support mental health after hospital discharge.

Guideline ratingSuggest FORCertainty: Low