Critique of the Surviving Sepsis Guidelines

Among the CICM examiners' most favourite punching bags, none are most prominently featured in the exam than the Surviving Sepsis guidelines. Trainees are usually invited to "critically evaluate" the guidelines - which means, describe their rationale, explain the pros and cons and give evidence to support their "own practice" statement. Because this has long been as staple of the Fellowship Exam, to score less than 7/10 is inexcusable for anybody who's done any amount of preparation for this test, and all future versions of these questions should be viewed as easy marks by the savvy candidates.

  • Question 1 from the first paper of 2014 required the candidates to generate a coherent ANZICS-themed response to the SSG and it was generally answered poorly.
  • Question 19 from the second paper of 2006 is analogous, but refers to the now-defunct 2003 version of the guidelines, which had even more problems.
  • The most recent guidelines have been interrogated in Question 12 from the second paper of 2015.
  • Given that in April 2018 the SSG updated their guidelines again (Levy et al, 2018), one could very reasonably expect to see an SAQ about this in the 2019 papers (allowing for the typical 18-month lag).

If one were too junior to generate their own opinion of the 2012 guidelines, where would one turn? Literature comes to the rescue with prefabricated opinions from experts.

More recent entries, relevant to the new 2018 SSG:

  • PulmCCM critique (harsh)
  • PulmCrit critique (harsher)
  • Pepper et al (2018), examining the evidence on which the SSG (and subsequent US performance measures) were based (spoiler: "few trials, poor-quality and confounded studies")

One could do worse than regurgitating these expert opinions in the exam. For one, some of the quoted experts might be the actual CICM examiners. To render easier the process of retention and disgorgement, these opinions are distilled in the discussion below.

In brief summary:

Advantages of SSG:

  • Good literature summary
  • GRADE system improves clarity
  • International panel of experts
  • Prevents ineficient variation in care
  • Some sort of "bundle synergy"

Disadvantages of SSG:

  • Bundles magnify ineffective therapies
  • GRADE system is subjective
  • Most recommendations are based on low-GRADE evidence
  • No evidence for any "bundle synergy"
  • Too much emphasis on EGDT

Evidence in support of SSG:

  • No evidence of harm from SSG use
  • In Australia, SSG-like care is provided anyway
  • Early antibiotics has good evidence to back it

Evidence against SSG:

  • ANZICS did not endorse
  • ProCESS,  ARISE and ProMISE studies did not demonstrate any survival benefit from protocolised care.

Now, in some detail:

Advantages of the SSG

High quality of the presented package

  • Excellent literature search and summary.
  • A good source of literature references
  • Well presented and easily accessible website.
  • Produced by an international panel of experts reviewing and grading the evidence.
  • GRADE system makes it easier for clinicians to assess the strength of a recommendation.

Evidence in defence of the guidelines

Criticisms of the SSG

Arguments against bundled care in general:

  • Marik et al: "Systematic promotion of evidence illustrates the power of bundles to magnify ineffective therapies."
  • All-or-none bundles may promote harmful therapies together with helpful ones. People end applying evidence-based treatment together with unsupported treatment. Remember Xigris, propagated by the SSG despite abundant evidence against its use.
  • There is no evidence that "bundle synergy" exists.
  • The quality of care might end up being measured according to bundle compliance, which is dangerously divorsed from actual "quality".

Objections on the basis of methodology:

  • Many of the recommendations are not based in high-level evidence
  • None of the recommendations are based in Level 1 evidence.
  • The GRADE system is subjective.

Objections to the guidelines themselves:

  • The guidelines digress significantly from sepsis, and creep across into other areas of ICU management.
  • Controversial recommendations are made, which may not be supported by evidence:
    • There is no survival benefit from routine ScvO2 monitoring (SSG authors agree)
    • There is no survival benefit from routine dobutamine use.
  • The emphasis on EGDT is not supported by strong evidence.

Objections to the evidence offered in support of widespread implementation:

  • All the trials demonstrating a benefit from SSG implementation were "before-and-after" trials.
    • These are chronically subject to publication bias, patient selection bias, temporal bias, and the Hawthorne effect.
  • All the trials tested the whole bundle, but frequently only one specific component was independently associated with a treatment effect (eg. early administration of antibiotics in the Edusepsis study from Spain)
  • The offered studies demonstrate a treatment effect in spite of poor adherence to the bundle (again Edusepsis - as an example mentioned by Marik et al - 5% decrease in mortality was attributed to the six-hour bundle, but the sites only complied with it 10% of the time).

Empirical evidence against the use of the guidelines:

 

References

Vo, Mai, and Jeremy M. Kahn. "Making the GRADE: how useful are the new Surviving Sepsis Campaign guidelines?." Critical Care 17.6 (2013): 328.

Marik, Paul E., Karthik Raghunathan, and Joshua Bloomstone. "Counterpoint: are the best patient outcomes achieved when ICU bundles are rigorously adhered to? No." CHEST Journal 144.2 (2013): 374-378.

Dellinger, R. Phillip, and Sean R. Townsend. "Rebuttal From Drs Dellinger and Townsend." CHEST Journal 144.2 (2013): 378-379.

Marik, Paul E., Karthik Raghunathan, and Joshua Bloomstone. "Rebuttal From Dr Marik et al." CHEST Journal 144.2 (2013): 379-380.

Chawla, Shalinee, and Jonas P. DeMuro. "Current controversies in the support of sepsis." Current opinion in critical care 20.6 (2014): 681-684.

Marik, Paul E. "Surviving sepsis: going beyond the guidelines." Annals of intensive care 1.1 (2011): 1-6.

Marik, Paul E. "Surviving sepsis." Critical care medicine 41.10 (2013): e292-e293.

Marik, Paul E. "Early management of severe sepsis: concepts and controversies." CHEST Journal 145.6 (2014): 1407-1418.

Kevin Klauer. "Sepsis: Unbundling the Bundle" in EP Monthly on May 24, 2012.

Priebe, Hans-Joachim. "Goal-directed resuscitation in septic shock." The New England journal of medicine 372.2 (2015): 189-189.

Kaukonen, Kirsi-Maija, et al. "Mortality related to severe sepsis and septic shock among critically ill patients in Australia and New Zealand, 2000-2012."Jama 311.13 (2014): 1308-1316.

Levy, Mitchell M., et al. "Outcomes of the Surviving Sepsis Campaign in intensive care units in the USA and Europe: a prospective cohort study." The Lancet infectious diseases 12.12 (2012): 919-924.

"Australia’s high survival rates shed doubt on global sepsis guidelines" - a press release by Monash University, home of ARISE.

Ferrer, Ricard, et al. "Improvement in process of care and outcome after a multicenter severe sepsis educational program in Spain." Jama 299.19 (2008): 2294-2303.

Barochia, Amisha V., et al. "Bundled care for septic shock: an analysis of clinical trials." Critical care medicine 38.2 (2010): 668.

Hicks, Peter, et al. "The surviving sepsis campaign: International guidelines for management of severe sepsis and septic shock: 2008. An assessment by the Australian and New Zealand Intensive Care Society." Anaesthesia and intensive care 36.2 (2008): 149-151. - this article was also published in Critical care and Resuscitation - and this version is available for free.

Levy, Mitchell M., Laura E. Evans, and Andrew Rhodes. "The surviving sepsis campaign bundle: 2018 update." Intensive care medicine (2018): 1-4.

IDSA Sepsis Task Force Kalil Andre C Gilbert David N Winslow Dean L Masur Henry Klompas Michael. "Infectious Diseases Society of America (IDSA) POSITION STATEMENT: Why IDSA Did Not Endorse the Surviving Sepsis Campaign Guidelines.Clinical Infectious Diseases 66.10 (2017): 1631-1635.

Napolitano, Lena M. "Sepsis 2018: Definitions and Guideline Changes." Surgical infections 19.2 (2018): 117-125.

Pepper, Dominique J., et al. "Evidence Underpinning the US Government–Mandated Hemodynamic Interventions for Sepsis: A Systematic Review." Annals of Internal Medicine(2018).