SSC 2026 — Part 1: Screening & Early Management

This section covers the initial recognition and early management of sepsis in adults, including institutional performance improvement programs, screening tools, biomarkers, blood cultures, lactate measurement, initial fluid resuscitation, the timing and route of vasopressor initiation, mean arterial pressure targets, and ICU admission timing. These recommendations apply to adults with possible, probable, or definite sepsis or septic shock in the emergency department, hospital ward, and prehospital settings.

1. Performance Improvement Programs

Recommendation 1 — Sepsis Performance Improvement Programs

For hospitals and health systems, we 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.

Strong recommendation

• Screening: moderate certainty evidence
• Standard operating procedures: very low certainty evidence
• Quality improvement strategies: strong recommendation, low certainty evidence

Change from 2021: Carried over (performance improvement program and screening); new (quality improvement strategies).

Rationale: Performance improvement programs and quality improvement strategies may vary by setting and in accordance with a hospital or health care system’s ability to implement. The 2021 SSC guidelines recommended using a performance improvement program for sepsis, including sepsis screening for acutely ill, high-risk patients and standard operating procedures for treatment.

Several relevant RCTs have been published since 2021. One RCT with 872 patients evaluated hour-1 bundle implementation in the emergency department and showed this standard operating procedure was associated with shorter time to antibiotics (73 min sooner; 95% CI, 93–53 min sooner) and an uncertain effect on mortality with a point estimate suggesting a possible large decrease (adjusted risk ratio [aRR] 0.81; 95% CI, 0.48–1.39).¹

Second, in the large stepped-wedge, cluster RCT SCREEN evaluating 60,055 patients, implementation of an electronic alert system, staff education, and feedback was associated with lower 90-day in-hospital mortality in patients with and without sepsis (aRR 0.85; 95% CI, 0.77–0.93).²

The recommendation for using quality improvement (QI) strategies was newly added. QI is a systematic and continuous effort to improve evidence-based care processes, such as timely antibiotic administration, with the aim of improving clinical outcomes. In a meta-analysis of 50 observational studies, sepsis QI initiatives were associated with improved delivery of recommended care practices and reduced mortality (odds ratio [OR] 0.66; 95% CI, 0.61–0.72). Furthermore, multiple before-and-after and differences-in-differences studies have shown improvements in both processes of care and clinical outcomes in hospitals participating in multi-hospital sepsis QI initiatives.

Key Implementation Elements:

• Sepsis screening protocols for acutely ill and high-risk patients
• Standardized treatment algorithms and order sets
• Regular performance auditing with data feedback
• Integration into existing antibiotic stewardship programs
• Adaptation to local resources and constraints

Recommendation 2 — Code Sepsis Protocols

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

Conditional recommendation, low certainty evidence

Change from 2021: New recommendation.

Rationale: “Code sepsis” is a multidisciplinary-driven process of care that aims to expedite the diagnosis and treatment of sepsis. While protocols vary, common elements include:

• A screening tool for tracking clinical indicators of suspected sepsis
• A trigger mechanism for alert activation (bedside clinician or automated algorithm)
• A response team providing immediate bedside evaluation and treatment

Composition of response teams varies widely — from dedicated multidisciplinary sepsis response teams, to general rapid response teams with sepsis expertise, to ad hoc teams of individuals already involved in the patient’s care (nurse, physician, pharmacist, unit manager).

Multiple interventional and observational studies with global representation investigating “code sepsis” were identified with mixed results in qualitative review. Several studies reported improved processes of care with the intervention, including lower mortality, reduced odds of mechanical ventilation, shorter time to administration of antibiotics and fluids, lower proportion of patients receiving vasopressors, and earlier escalation of care. Furthermore, in the SCREEN trial evaluating 60,055 patients, implementation of an electronic alert system, staff education, and feedback was associated with lower 90-day in-hospital mortality (aRR 0.85; 95% CI, 0.77–0.93).²

The benefit extends to patients not found to have sepsis by mitigating morbidity and mortality through early identification of patients at risk for clinical deterioration and worse outcomes. Implementing a code sepsis protocol may provide more benefit in settings with less robust infrastructure for sepsis recognition and treatment, but relatively less incremental benefit in settings that already have robust systems in place to rapidly identify and treat sepsis.

2. Prehospital Screening

Recommendation 3 — Prehospital Sepsis Screening

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

Conditional recommendation, very low certainty evidence

Change from 2021: New recommendation.

Rationale: Sepsis treatment is time-sensitive, and for the one-half of sepsis patients transported to hospitals by ambulance, the prehospital period is an opportunity to identify sepsis and initiate hospital notification and treatment. Using prehospital sepsis screening tools to identify patients at high risk for sepsis and sepsis-related death could shorten time to treatment and improve clinical outcomes. Prehospital notification has improved timeliness of care in other acute care conditions, and diagnostic momentum initiated through ambulance screening and pre-arrival notification can improve sepsis performance.

In a scoping review and a separate systematic review of prehospital sepsis screening tools, all had moderate ability to identify patients with sepsis in the prehospital environment. In a comparative study of 221,429 prehospital medical records, the following early warning scores were evaluated:

NEWS2 had the best absolute test performance of studied screening tools. However, due to lower specificity (81.6%, 95% CI, 80.4–82.7%), high rate of false-positive screens (positive predictive value 6.5%, 95% CI, 5.8–7.3%), and perceived difficulty of use in the prehospital environment, the panel refrained from recommending a specific screening tool. qSOFA had the lowest prehospital sepsis sensitivity.

The use of a prehospital screening tool is likely feasible and adaptable in all geographic settings and should be a research priority in low resource settings.

3. In-Hospital Screening

Recommendation 4 — Hospital Screening Tools

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

Strong recommendation, moderate certainty evidence

Change from 2021: Revisited.

Rationale: The Sepsis-3 task force identified qSOFA as a predictor of death or prolonged ICU stay in patients with known or suspected infection, but no analysis had been performed at that time to support its use as a screening tool. The 2021 SSC guidelines recommended against qSOFA as a sole sepsis screening tool. Since then, numerous studies have investigated its use as a screening tool, with consistent findings.

Four systematic reviews and meta-analyses have reported that Early Warning Scores (EWS), including NEWS, NEWS2, MEWS, and SIRS were more sensitive for the diagnosis of sepsis than qSOFA. Similar findings have been reported in LMICs.

There is no ideal tool to screen for sepsis that has both high sensitivity and specificity. Screening tools should have high sensitivity to limit the number of false negative results. A large cohort study of over 221,000 patients demonstrated NEWS2 had the greatest sensitivity and specificity compared with MEWS, SIRS, and qSOFA. EWS were designed to identify patients at risk of clinical deterioration from a variety of causes, and as such, they perform well in assisting with the identification of sepsis.

Key point: qSOFA, while having lower sensitivity for sepsis than other tools, is still useful for detecting clinical deterioration. A recently published stepped wedge trial showed that electronic qSOFA screening with activation of an alert system triggering subsequent nurse and physician assessment and interventions resulted in improved 90-day mortality, including in non-septic patients.²

The use of artificial intelligence (AI) is receiving increasing attention as a tool for early screening and prediction of sepsis. Future research may inform practice in this area and should involve comparative studies.

Recommendation 5 — Biomarkers and Rapid Diagnostics

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

Good practice statement

Change from 2021: New.

Rationale: Several novel host response diagnostic tests are approved by regulatory bodies and available as diagnostic aids for sepsis. These tests use several approaches to assess a patient’s likelihood of having or developing sepsis:

• WBC characteristics: Monocyte distribution width (MDW) and IntelliSep evaluate circulating monocyte and neutrophil characteristics
• Messenger RNA transcripts: SeptiCyte Rapid and TriVerity assess messenger RNA transcripts associated with infection and sepsis; TriVerity also distinguishes viral vs. bacterial infection
• AI-based approaches: Sepsis ImmunoScore combines EHR data with biomarker and cytokine measurements
• Serum biomarkers: Pancreatic stone protein and others

None of these novel host response diagnostics provides a “positive” or “negative” result. Instead, they categorize the post-test risk of sepsis into categories (e.g., low, medium, high). The post-test likelihood ratios are not uniform across tests, and clinicians should familiarize themselves with individual test characteristics before use. None of the tests should be considered definitive; all should be used in combination with a full clinical evaluation.

Due to the costs of these diagnostic aids, lack of evidence that they improve patient-centered outcomes or resource utilization, the panel did not recommend the use of any specific sepsis diagnostic aid.

Recommendation 6 — Novel Host Response Diagnostics

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

No recommendation

Change from 2021: New.

4. Blood Cultures

Recommendation 7 — Blood Culture Collection

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

Strong recommendation, low certainty evidence

Change from 2021: New (upgraded from best practice statement).

Rationale: Identifying the causative organism in sepsis helps to optimize antimicrobial therapy, ensure that the causative pathogen is treated, support antimicrobial stewardship, and improve patient outcomes. A pathogen is identified in approximately 60–70% of patients with sepsis, although blood cultures are positive in only approximately 10–20% of patients.

Several factors affect the yield of blood cultures:

In a multicenter study of 325 patients presenting to the emergency department with sepsis-induced hypotension or hypoperfusion (SBP < 90 mm Hg or lactate ≥ 4 mmol/L), blood culture positivity decreased from 31.4% pre-antimicrobial to 19.4% at a median 70 minutes (IQR, 50–110 min) post-antimicrobial, a 12.0% absolute reduction and 38.2% relative reduction in blood culture sensitivity.

Clinical guidance:

• Collect cultures from two different sites using 10 mL blood volume per tube
• Multi-site collection is recommended to distinguish pathogens from contaminants and increase sensitivity
• In low resource settings, collection of a single set of blood cultures can be justified based on a 2025 systematic review showing similar yield between single vs. multiple blood culture sets
• Do not delay antimicrobial therapy for blood culture collection, particularly in patients with hypotension
• Repeat cultures are recommended to confirm clearance of bacteremia or fungemia for Staphylococcus aureus, Staphylococcus lugdunensis, and Candida species
• Additional site-specific cultures (e.g., peritoneal fluid culture) should be considered depending on the suspected source of infection

5. Lactate Measurement

Recommendation 8 — Blood Lactate

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

Conditional recommendation, low certainty evidence

Change from 2021: Carryover.

Rationale: This statement on performance was carried over; please see the 2021 SSC guidelines for rationale.³ Serum lactate is an indirect and nonspecific marker of global tissue perfusion, and elevated levels (≥ 2 mmol/L) are independently associated with increased mortality. Venous and arterial lactate levels are clinically interchangeable for screening purposes.

6. Initial Fluid Resuscitation

Recommendation 9 — Sepsis as a Medical Emergency

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

Good practice statement

Change from 2021: Carryover.

Recommendation 10 — Initial Crystalloid Volume

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

Conditional recommendation, low certainty evidence

Change from 2021: Revisited (with new remarks).

Rationale: Consistent with 2016 and 2021 SSC guidelines, the panel suggests administering at least 30 mL/kg of IV crystalloids for initial fluid resuscitation in patients with sepsis-induced hypoperfusion or septic shock. Sepsis-induced hypoperfusion may be identified by hypotension (MAP < 65 mm Hg, SBP < 90 mm Hg, relative hypotension), or elevated lactate. Although lactate > 4 mmol/L has historically been the threshold for fluid-resuscitation, intermediate lactate elevation (> 2 to < 4 mmol/L) is common in patients with sepsis, is associated with increased mortality, and may also benefit from fluid-resuscitation to avoid progression to overt hypoperfusion or shock.

The fixed volume of 30 mL/kg is based on observational evidence, with most studies using actual body weight. There are no prospective interventional studies comparing different volumes for initial resuscitation in sepsis or septic shock. A retrospective analysis showed that failure to receive 30 mL/kg within 3 hours of sepsis onset was associated with increased odds of in-hospital mortality, delayed resolution of hypotension, and increased ICU length of stay. A recent systematic review and meta-analysis reported that a survival benefit was observed when 30 mL/kg was completed within 3 hours (low certainty).

30 mL/kg in Liters, by Weight and Height:

White cells: BMI ≤ 30 kg/m² — display 30 mL/kg using actual body weight. Italicized values: BMI > 30 kg/m² — display 30 mL/kg using adjusted body weight. Adjusted Body Weight = Ideal Body Weight + 0.4 × (Actual Body Weight − Adjusted Body Weight), where Ideal Body Weight was calculated using the Devine formula.

Remarks:

• Consideration should be given to individual patient characteristics and context when selecting initial fluid volume
• Clinicians prescribing fluids should perform frequent, ongoing reassessment and closely monitor patients to avoid harms of under- or over-resuscitation
• Weight-based fluid volume should be calculated based on actual body weight, or by adjusted or ideal body weight in patients with BMI > 30 kg/m²

7. Timing of Vasopressor Initiation

Recommendation 11 — Vasopressor Timing Relative to Fluids

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

Conditional recommendation, very low certainty evidence

Change from 2021: New.

Rationale: Sepsis-induced hypotension is a critical condition that requires prompt and appropriate intervention to restore perfusion and mitigate the risk of end-organ damage. The timing of vasopressor initiation — either immediately, concomitantly with, or after fluid resuscitation — remains a topic of debate.

The rationale for earlier vasopressor initiation includes faster restoration of blood pressure and prevention of fluid overload. Persistent hypotension is associated with worse outcomes in observational studies. Recent studies provide mixed evidence on the timing of vasopressor administration in sepsis-induced hypotension.

Two small, single-center RCTs suggest that early administration of fixed, low-dose norepinephrine is associated with reduced fluid requirements and lower short-term mortality. However, the multicenter CLOVERS RCT found no difference in 90-day mortality, organ support-free days, or receipt of invasive ventilation between resuscitation algorithms with early vs. delayed vasopressor initiation.

Remark: In patients with unstable septic shock, immediate concurrent administration of vasopressors together with IV crystalloid fluid may be warranted on a case-by-case basis. Presence of unstable shock should be determined by physical exam. Suggestive clinical features include severely reduced blood pressure, mottled skin, ashen appearance, cyanosis/decreased oxygen saturation, tachycardia, and altered mentation.

8. Route of Vasopressor Administration

Recommendation 12 — Peripheral Vasopressor Initiation

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

Conditional recommendation, very low certainty evidence

Change from 2021: Revisited.

Rationale: Traditionally, vasopressors were administered exclusively through central venous catheters out of concern for tissue necrosis associated with extravasation from peripheral IV lines. Recent data suggest that clinicians and hospital policies are more comfortable with peripheral vasopressor administration than with delayed initiation of vasopressors if no central access is present.

The panel considered one RCT of 263 general ICU patients (of whom 70% required vasopressors) randomized to immediate central venous catheter placement vs. no catheter placement, which found an uncertain effect on mortality (HR 1.30; 95% CI, 0.84–2.01, very low certainty evidence). Across seven studies (1,657 patients), the pooled complication rate for peripheral vasopressor administration was 5.97% (95% CI, 1.17–14.09%, very low certainty).

“In our practice,” 86.6% of panel members use peripheral vasopressors on at least some occasions. Nearly one-half (46.6%) use peripheral vasopressors for up to 6 hours, 13.8% use them for up to 24 hours, and 27.6% do not have a set duration for use.

Remark: Data are insufficient to recommend a duration of use, dose, or access route (size of peripheral IV line or anatomic location). Midline catheters were not considered.

9. Mean Arterial Pressure Targets

Recommendation 13 — MAP Target: General Population

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

Strong recommendation, moderate certainty evidence

Change from 2021: Carryover (with new remark).

Remark: In practice, it is not feasible to maintain MAP at exactly 65 mm Hg, so a reasonable range (e.g., within 5 mm Hg) should be used. Vasopressors should be titrated to maintain MAP within this range.

Recommendation 14 — MAP Target: Elderly Patients

For adults with septic shock 65 years old or older, we suggest an initial MAP range of 60–65 mm Hg over higher ranges.

Conditional recommendation, low certainty evidence

Change from 2021: New.

Rationale: Mean arterial pressure is a key determinant of mean systemic filling pressure, which in turn is a major driver of venous return and cardiac output. MAPs below a threshold of approximately 60 mm Hg are associated with decreased organ perfusion.

The 2021 SSC guidelines recommended targeting an MAP of 65 mm Hg or higher for initial resuscitation, based principally on an RCT in septic shock comparing a MAP target of 65–70 mm Hg vs. 80–85 mm Hg, which found no difference in mortality between arms, although a subgroup analysis demonstrated a 10.5% absolute reduction in renal replacement therapy with higher MAP targets among patients with chronic hypertension. However, targeting a higher MAP was associated with a higher risk of atrial fibrillation.

A meta-analysis of two RCTs indicated that higher MAP targets may result in little to no difference in short-term mortality (RR, 1.05; 95% CI, 0.90–1.23, low certainty). One RCT subsequently compared “permissive hypotension” (MAP 60–65 mm Hg) to “usual care” in patients 65 years and older with distributive shock. The intervention arm achieved a mean MAP of 67 mm Hg vs. 73 mm Hg in the usual care arm. Ninety-day mortality was similar (41.0% vs. 43.8%). An open-label trial of 518 patients ≥ 65 years comparing lower BP target (MAP 65–70 mm Hg) vs. higher (MAP 80–85 mm Hg) reported increased mortality associated with the higher MAP target.

In the absence of data to support a higher MAP target, the panel makes a new conditional recommendation for an initial MAP target of 60–65 mm Hg in adults 65 years or older.

10. ICU Admission Timing

Recommendation 15 — ICU Admission Within 6 Hours

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

Conditional recommendation, low certainty evidence

Change from 2021: Carryover.

Rationale: This statement was carried over; please see the 2021 SSC guidelines for rationale.³

Quick Reference: Screening & Early Management Summary

SCREENING & EARLY MANAGEMENT — AT A GLANCE

1. INSTITUTIONAL PROGRAMS
   ✓✓ Performance improvement program with screening, SOPs, QI     [Strong]
   ✓  Code sepsis / sepsis huddle protocol                        [Conditional]

2. SCREENING
   ✓  Prehospital: use a standard sepsis screening tool           [Conditional]
   ✓✓ In-hospital: use NEWS/NEWS2/MEWS/SIRS over qSOFA           [Strong]
   GPS Sepsis cannot be ruled in/out by a single biomarker        [GPS]
   —  Novel host response diagnostics: insufficient evidence      [No rec]

3. DIAGNOSTICS
   ✓✓ Blood cultures ASAP, ideally before antimicrobials           [Strong]
   ✓  Measure blood lactate                                       [Conditional]

4. INITIAL RESUSCITATION
   GPS Sepsis is a medical emergency — treat immediately          [GPS]
   ✓  ≥ 30 mL/kg IV crystalloid in first 3 hours                  [Conditional]

5. VASOPRESSORS
   ✓  IV crystalloid bolus first → vasopressor if hypotension persists  [Conditional]
   ✓  Start vasopressors peripherally if no central access         [Conditional]

6. MAP TARGETS
   ✓✓ Target MAP ≥ 65 mm Hg (general population)                  [Strong]
   ✓  Target MAP 60-65 mm Hg (age ≥ 65 years)                     [Conditional]

7. ICU ADMISSION
   ✓  Admit to ICU within 6 hours when ICU care is required        [Conditional]

KEY: ✓✓ = Strong recommendation ("we recommend")
     ✓  = Conditional recommendation ("we suggest")
     GPS = Good practice statement
     —  = No recommendation / insufficient evidence

References