Question 12

Outline the strengths and limitations of the current Surviving Sepsis Campaign Guidelines, using examples to illustrate your points.

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College Answer


The guidelines are formulated by an international panel of experts reviewing and grading the evidence.

Use of the Grading of Recommendations Assessment Development and Evaluation (GRADE) for guideline development.

o GRADE separates the assessment of the quality of the evidence from the ultimate strength of the recommendations (allows for strong recommendations when the quality of evidence is weak or weak recommendations when the quality of evidence is strong, particularly when patient values and preferences may strongly factor into the equation).

Intensivists may use as a decision-making tool in their practice as: Information to aid practice

An established source of references Reduce variations in clinical practice

The current recommendations may generate areas for future research and consensus statements for this high-risk and high-cost patient group.


The GRADE system, although transparent, is still subjective. Recommendations depend greatly on the values and preferences of the committee members.

Guidelines attempt to include nearly every aspect of critical care potentially related to sepsis, thereby losing focus in the process and becoming a general ICU guideline.

A narrower guideline dedicated to sepsis-specific management might be more useful. Complexity and diversity of sepsis may defy a single guideline for all cases.

Guidelines may rapidly become out-dated

E.g. the 2012 guidelines on prone positioning for patients with PaO2/FiO2 ratios < 100 despite such manoeuvres (Grade 2C). This would now potentially be (1B)

Recommends use of proton pump inhibitors over histamine-2 receptor antagonist for stress ulcer prophylaxis (grade 2C), although the emerging consensus suggests that this approach may not be beneficial and indeed may even be harmful.

There are recommendations that may be considered controversial

E.g. Conservative fluid strategy in patients with sepsis-induced adult respiratory distress syndrome in the absence of evidence of tissue hypo perfusion (grade 1C)

The guidelines emphasize ‘bundles’ of care for sepsis resuscitation, although the evidence behind some of the bundled recommendations is not strong, for example using central venous pressure readings to guide volume resuscitation.

Significant risk that bundles will be utilised as quality measures with which Intensivist (who may validly disagree with some of the recommendations) treating sepsis will be assessed/benchmarked.


Again, this was brought up in the wake of three recent publications. The increasingly mindless rote-learned answer to these multiplying questions is offered below, and is largely identical to the discussion sections of Question 19 from the second paper of 2006 and Question 1 from the first paper of 2014.

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:


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.