Rebuttal From Drs Marik, Farkas, Spiegel et al

      Levy et al
      • Levy M.M.
      • Rhodes A.
      • Evan L.E.
      for the Steering and Executive Committee of the Surviving Sepsis Campaign
      Counterpoint: Should the Surviving Sepsis Campaign guidelines be retired? No.
      referenced 13 studies to support the Surviving Sepsis Campaign (SSC). On careful review, none of these studies provide robust scientific evidence that SSC has improved mortality.
      • Pepper D.J.
      • Jaswal D.
      • Sun J.
      • Natanson C.
      • Eichacker P.Q.
      • et al.
      Evidence underpinning the Centers for Medicare & Medicaid Services’ Severe Sepsis and Septic Shock Management Bundle (SEP-1): a systematic review.
      In fact, they highlight the lack of solid evidence supporting the SSC.
      Some studies used a quasiexperimental design to compare outcomes before vs after implementation of sepsis guidelines.
      • Castellanos-Ortega A.
      • Suberviola B.
      • Garcia-Astudillo L.A.
      • et al.
      Impact of the Surviving Sepsis Campaign protocols on hospital length of stay and mortality in septic shock patients: results of a three-year follow-up quasi-experimental study.
      Although improved outcomes are an optimistic sign, this may easily be explained by greater attention and energy for sepsis therapy (the Hawthorne Effect).
      Several articles correlate the receipt of various interventions with mortality.
      • Seymour C.W.
      • Gesten F.
      • Prescott H.C.
      • et al.
      Time to treatment and mortality during mandated emergency care for sepsis.
      Such correlations are laden with confounding factors; for example, compliance with the sepsis bundle is a surrogate marker for a patient receiving more aggressive management overall. Prompt receipt of interventions could reflect that the patient is otherwise healthy and thus more rapidly diagnosed with sepsis. Quite simply, correlational studies cannot prove causation.
      Decreasing sepsis mortality over several years has been interpreted as evidence to support the success of the SSC, but parallel mortality reductions have been noted in Australia and New Zealand despite rejection of SSC by those countries.
      • Kaukonen K.M.
      • Bailey M.
      • Suzuki S.
      • Pilcher D.
      • Bellomo R.
      • et al.
      Mortality related to severe sepsis and septic shock among critically ill patients in Australia and New Zealand, 2000-2012.
      Improving outcomes therefore likely reflect gradual improvements in critical care over time.
      In addition to these observational data, four multicenter randomized clinical trials (RCTs) were referenced. None support the SSC. Prospective Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis in Adult Patients With Septic Shock disproved the utility of activated protein C, which was recommended by the SSC at that time.
      • Ranieri V.M.
      • Thompson B.T.
      • Barie P.S.
      • et al.
      Drotrecogin alfa (activated) in adults with septic shock.
      The Protocolized Care for Early Septic Shock, Australasian Resuscitation in Sepsis Evaluation, and Protocolised Management in Sepsis trials uniformly disproved the necessity of invasive early goal-directed therapy, a cornerstone of the SSC treatment bundles at that point. When components of SSC were subjected to rigorous scientific testing, they were therefore found to be therapeutically ineffective.
      Overall, these studies show a dramatic schism between multicenter RCTs (which have consistently disproven SSC guidelines) vs observational trials (which seem to support the SSC guidelines). This disconnect is remarkable because most of the observational trials supporting SSC were performed using invasive early goal-directed therapy, a treatment that has currently been discarded. Overall, this demonstrates that no matter how optimistic observational studies may seem, rigorous RCTs are required to provide truly scientific evidence. Guideline-driven health care policy should never be based upon retrospective, correlational studies.
      No evidence seems to exist supporting the 1-h cutoff recommended in the 2018 revised SSC bundle. Collapse of the 3- and 6-h bundles into a single 1-h bundle is an enormous change, which appears to be completely arbitrary. No data are provided to show that implementing a 1-h bundle is either feasible or beneficial.
      We agree with Levy et al
      • Levy M.M.
      • Rhodes A.
      • Evan L.E.
      for the Steering and Executive Committee of the Surviving Sepsis Campaign
      Counterpoint: Should the Surviving Sepsis Campaign guidelines be retired? No.
      that sepsis is a medical emergency warranting immediate and aggressive management; however, we also believe that strong recommendations by international guidelines must be based upon robust, validated scientific evidence. The SSC guidelines openly admit failure to do so (eg, recommendations for fluid management are listed as a strong recommendation based upon weak evidence). We therefore support the moratorium placed upon the 2018 SCC bundles by the SCCM and ACEP.

      Acknowledgments

      *Collaborating authors: Scott Aberegg, MD, MPH, University of Utah, UT; Jennifer Beck-Esmay, MD, Mount Sinai Saint Luke’s-West; Steven Carroll, DO, MEd, Emory University School of Medicine, GA; Jon-Emile Kenny, MD; Alex Koyfman, MD, FACEP, FAAEM, UT Southwestern Medical Center, TX; Michelle Lin, MD, University of California, CA; Brit Long, MD, Brooke Army Medical Center, TX; Manu Malbrain, MD, PhD, Brussels University Hospital (UZB), Belgium; Justin Morgenstern, MD, University of Toronto, Canada; Segun Olusanya, MD, St Bartholomew’s Hospital, UK; Salim Rezaie, MD, Greater San Antonio Emergency Physicians, TX; Philippe Rola, MD, Montreal Canada; Manpreet Singh, MD, Harbor-UCLA Medical Center, CA; Reuben Strayer, MD, Anand Swaminathan, MD; and Adam Thomas, MD, FRCPC, University of British Columbia, Canada.

      References

        • Levy M.M.
        • Rhodes A.
        • Evan L.E.
        • for the Steering and Executive Committee of the Surviving Sepsis Campaign
        Counterpoint: Should the Surviving Sepsis Campaign guidelines be retired? No.
        Chest. 2019; 155: 14-17
        • Pepper D.J.
        • Jaswal D.
        • Sun J.
        • Natanson C.
        • Eichacker P.Q.
        • et al.
        Evidence underpinning the Centers for Medicare & Medicaid Services’ Severe Sepsis and Septic Shock Management Bundle (SEP-1): a systematic review.
        Ann Intern Med. 2018; 168: 558-568
        • Castellanos-Ortega A.
        • Suberviola B.
        • Garcia-Astudillo L.A.
        • et al.
        Impact of the Surviving Sepsis Campaign protocols on hospital length of stay and mortality in septic shock patients: results of a three-year follow-up quasi-experimental study.
        Crit Care Med. 2010; 38: 1036-1043
        • Seymour C.W.
        • Gesten F.
        • Prescott H.C.
        • et al.
        Time to treatment and mortality during mandated emergency care for sepsis.
        New Engl J Med. 2017; 376: 2235-2244
        • Kaukonen K.M.
        • Bailey M.
        • Suzuki S.
        • Pilcher D.
        • Bellomo R.
        • et al.
        Mortality related to severe sepsis and septic shock among critically ill patients in Australia and New Zealand, 2000-2012.
        JAMA. 2014; 311: 1308-1316
        • Ranieri V.M.
        • Thompson B.T.
        • Barie P.S.
        • et al.
        Drotrecogin alfa (activated) in adults with septic shock.
        N Engl J Med. 2012; 366: 2055-2064

      Linked Article

      • POINT: Should the Surviving Sepsis Campaign Guidelines Be Retired? Yes
        CHESTVol. 155Issue 1
        • In Brief
          Concern regarding the Surviving Sepsis Campaign (SSC) guidelines dates to their inception. Guideline development was sponsored by Eli Lilly and Edwards Life Sciences as part of a commercial marketing campaign.1 Throughout its history, the SSC has a track record of making strong recommendations based on weak evidence and being poorly responsive to new evidence.2-4 The original backbone of the guidelines was a single-center trial by Rivers et al5 defining a protocol for early goal-directed therapy.
        • Full-Text
        • PDF
      • COUNTERPOINT: Should the Surviving Sepsis Campaign Guidelines Be Retired? No
        CHESTVol. 155Issue 1
        • In Brief
          To address the question at the core of this Point/Counterpoint, the Surviving Sepsis Campaign (SSC) guidelines must be considered separately from the SSC bundles because they are distinctly different entities. We will explain why neither the guidelines nor the bundles should be abandoned based on the clear published data that demonstrate the benefit to patient care of both applying the guidelines and adhering to the bundles. Further, because the history of SSC has been marked by controversy, we will attempt to distinguish between academic debate and clinical impact on patient care and outcomes.
        • Full-Text
        • PDF