Sepsis-3: New Definition Impacts Guidelines and Practices

Tuesday, September 5, 2017

William Alvarez, Jr., PharmD, BCPS, and Christine M. Cohn, PharmD, BCPS

September is Sepsis Awareness Month. Follow events and discussions at #SAM2017.

According to the Sepsis Alliance, every 2 minutes someone in the U.S. dies from sepsis.

This is not news to healthcare professionals, especially those in critical care. In an effort to reduce mortality and speed administration of life-saving therapies, the American College of Chest Physicians and Society of Critical Care Medicine developed a set of definitions and care guidelines for sepsis in 1991.

Some elements of those definitions were expanded in 2001, and the new guidelines became known as Sepsis-2.

Recently, the third convening of the task force led to the publication of Sepsis-3. These current revisions to the guidelines attempt to differentiate between sepsis and non-complicated infection and to promote early diagnosis and rapid implementation of treatment.

Some clinicians believe that the Sepsis-3 definitions are still a work in progress. The Centers for Medicare & Medicaid Services (CMS), for example, are still using previous definitions.

Narrower Definition Sparks Concerns

The new definitions eliminate the terms systemic inflammatory response syndrome (SIRS), since the cause of SIRS is not always infection, and “severe sepsis.” The following definitions have also been revised:

  • Sepsis is now defined as life-threatening organ dysfunction caused by a dysregulated host response to infection
  • Organ dysfunction is now defined in terms of change in baseline sequential organ failure assessment (SOFA) score
  • Septic shock is now defined as a subset of sepsis in which the patient experiences circulatory and cellular/metabolic abnormalities (has a higher risk of mortality)

The concern that has arisen among clinicians is that, while Sepsis-3 may eliminate inappropriate diagnosis of sepsis in patients with SIRS who do not have infection, early diagnosis of sepsis may be missed, as the definitions no longer include the concept of sepsis without organ dysfunction. Even though mortality risk in these patients is lower, they are likely to benefit from early treatment. And even though their condition may be less severe, a risk of mortality does still exist for these patients now excluded from the sepsis definition.

There is also concern about the new definitions when it comes to identifying more severely affected patients — those experiencing septic shock.

A 2017 study in Critical Care Medicine reported that 57% of patients studied who met the criteria for septic shock under Sepsis-1 definitions did not meet the criteria under Sepsis-3. While the study found that Sepsis-3 criteria was successful in identifying patients with high-risk organ failure and greater risk of mortality, those it excluded still experienced organ failure and a 14% mortality rate.

Nonetheless, when it comes down to the point of care, clinicians are going to rely on their experience and consider the parameters of the individual case at hand to inform their treatment decisions, whether or not their patients tick all the right boxes of the Sepsis-3 definitions.

Practice Changes

In addition to the new definitions and criteria for diagnosis, Sepsis-3 revised several treatment recommendations and best practices.

The major recommendations include:

  • New assessment tools, such as evaluating SOFA/qSOFA instead of SIRS criteria
  • Removal of early goal-directed therapy (EGDT) resuscitation targets in favor of a recommendation for a fixed volume of fluid to be administered (within the first 3 hours) to patients with sepsis-induced hypoperfusion
  • Recommended use of empiric broad spectrum antibiotics (e.g., vancomycin and piperacillin/tazobactam)
  • Recommendation against double coverage for ongoing treatment of most other serious infections
  • Measurement of procalcitonin levels to support shortening of duration of antimicrobial therapy, as appropriate, in patients with sepsis
  • Recommendation against high frequency oscillatory ventilation (HFOV)
  • Removal of pediatric recommendations — they will now be published in a separate document

Treating Sepsis

Broad spectrum antibiotics are recommended to treat sepsis initially with de-escalation within the first few days as the patient clinically improves. When determining which broad spectrum antibiotics and other medications are best suited to treating septic patients, clinicians should consider a number of factors:

  • Site of infection
  • Age
  • Presence of indwelling devices
  • Underlying chronic disease/organ dysfunction
  • Presence of immunosuppression or other form of immunocompromise
  • Recent infections or colonization
  • Antimicrobial exposure in the past 3 months
  • Patient’s location at time of infection onset (e.g., hospital, long-term care facility, community)
  • Local pathogen prevalence and susceptibility patterns
  • Potential drug intolerance and toxicity

Sepsis is a tricky medical issue. Even after the guidance issued by task force in its three meetings, severity and rate of sepsis has increased. But, while mortality rate in patients with sepsis continues to be high, the overall mortality rate seems to be decreasing.

Although evidence is conflicting, this progress is possibly due to improved treatment strategies. Clinical decision support solutions assist clinicians in following task force recommendations for sepsis treatment. For example, Lexicomp electronic drug reference contains updated Sepsis-3 guidelines in all relevant drug monographs and infectious disease topics. This allows clinicians on the front lines to have easy access to the recommended diagnosis and treatment best practices to support better outcomes and continued improvement in sepsis mortality rates.

William Alvarez, Jr., PharmD, BCPS, is one of the clinical managers within Core Pharmacology division of Wolters Kluwer Clinical Drug Information, specializing in cardiovascular medicine and critical care. He has been an active contributor for 10 years and oversees a clinical team responsible for the development of clinical drug information for Wolters Kluwer solutions.

Christine M. Cohn, PharmD, BCPS, is a senior clinical content specialist in infectious diseases for Wolters Kluwer Clinical Drug Information. She has been part of the Clinical Drug Information content team for 9 years.

Want to learn more about sepsis? Check out this RxPerts Academy feature:

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