By Dean L. Winslow, MD, MACP, FIDSA, FPIDS

Professor of Medicine, Division of General Medical Disciplines, Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine

SYNOPSIS: The Surviving Sepsis Guidelines (last updated in 2016) have just been updated. Some of the important changes include clearer differentiation of sepsis vs. septic shock and, for many recommendations, changing the strength of recommendation and quality of evidence to support many recommendations.

SOURCE: 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:e1063-e1143.

This paper reflects the work of dozens of co-authors from both the Society of Critical Care Medicine and the Infectious Diseases Society of America (IDSA). Some of the important changes from the 2016 Surviving Sepsis Guidelines are detailed in Table 1 of this 81-page paper containing 653 references.1 These changes include:

  1. The quick sepsis related organ failure assessment (qSOFA) score now is recommended as the best sepsis screening tool.
  2. Blood lactate measurements now are considered a weak recommendation with low quality of evidence.
  3. The previous strong recommendation for giving patients with sepsis initial fluid administration of 30 mL/kg has been downgraded to weak with lowquality of evidence.
  4. Use of capillary refill time as an adjunctive means of assessment of perfusion has been added as a weak recommendation with low quality of evidence.
  5. Administration of antibiotics within one hour of presentation for both possible sepsis and septic shock has been changed to recommending this only for septic shock or sepsis where likelihood of infection is high.
  6. Administration of antibiotics within three hours for possible sepsis without shock has been downgraded from a strong to a weak recommendation.
  7. A new recommendation for adults with a low likelihood of infection and without shock is that it is now suggested to defer antimicrobials while continuing to monitor the patient closely.
  8. A best practices statement in the 2021 guidelines now states that in adult patients thought to be at high likelihood of harboring methicillin-resistant Staphylococcus aureus (MRSA), appropriate antibiotics targeting MRSA should be given rather than the previous recommendation to give broad-spectrum antibiotics.
  9. Similarly, for adult patients considered to be at high risk for being infected with fungal pathogens, it now is recommended that empiric antifungal coverage be given, rather than the previous recommendation to cover all possible pathogens.
  10. Balanced crystalloids, rather than normal saline, now are recommended for resuscitation.
  11. Gelatin is no longer recommended for resuscitation.
  12. For adults with septic shock, it is recommended to start vasopressors peripherally rather than waiting for a central line to be placed.
  13. The new guidelines state that there is little evidence to support a restrictive vs. liberal fluid infusion strategy after initial fluid resuscitation.
  14. For adults with sepsis-induced hypoxemic respiratory failure, it now is suggested to use high-flow nasal oxygen over noninvasive ventilation.
  15. For adults with sepsis-induced severe acute respiratory distress syndrome (ARDS), the new guidelines suggest using veno-venous (VV) extracorporeal membrane oxygenation (ECMO) when conventional mechanical ventilation fails in experienced centers with the infrastructure in place to support its use.
  16. For adults with septic shock and an ongoing requirement for vasopressor therapy, the 2021 guidelines suggest using intravenous (IV) corticosteroids.


The 2021 revision of the Surviving Sepsis Guidelines are a big improvement over the 2016 version. Readers may remember that many of the recommendations in the 2016 Surviving Sepsis Guidelines were not supported by evidence, yet were made with an often strong recommendation level. This resulted in the IDSA withdrawing its support for the guidelines.2

The 2021 guidelines now highlight areas of uncertainty and also clearly differentiate between septic shock (where rapid administration of antibiotics and appropriate fluid resuscitation are critical to survival) vs. “sepsis” without septic shock, where the potential harms of inappropriate antibiotic administration and overly aggressive fluid resuscitation may cause signifi-cant harm.3 Unfortunately, the Centers for Medicare and Medicaid Services SEP-1 quality bundles do not yet reflect the now nuanced and evidence-backed Surviving Sepsis Guidelines. Because many hospital quality improvement programs are tied to SEP-1 bundle compliance, this likely still will cause many patients to receive inappropriate antibiotics, excessive fluid resuscitation, and other inappropriate treatment. Recently IDSA has recommended changes to these SEP-1 quality measures as well.4 


  1. Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: International guidelines for management of sepsis and septic shock: 2016. Crit Care Med 2017;45:486-552.
  2. Gilbert D, Kalil A, Klompas M, et al. Infectious Diseases Society of America (IDSA) position statement: Why IDSA did not endorse the Surviving Sepsis Campaign guidelines. Clin Infect Dis 2018;66:1631-1635.
  3. Swenson KE, Winslow DL. Impact of sepsis mandates on sepsis care: Unintended consequences. J Infect Dis 2020;222(Suppl 2):S166-S173.
  4. Rhee C, Chiotos K, Cosgrove SE, et al. Infectious Diseases Society of America position paper: Recommended revisions to the National Severe Sepsis and Septic Shock Early Management Bundle (SEP-1) sepsis quality measure. Clin Infect Dis 2021;72:541-552.