Question 1

College Answer

Strengths:

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

Limitations

• 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)
• Early Goal Directed Therapy (EGDT) is strongly recommended, but potentially has a limited evidence base.
• 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 intensivists (who may validly disagree with some of the recommendations) treating sepsis will be assessed/benchmarked.

Examiners' comments: Candidates appeared to have a lack of understanding of the SSC Guidelines and were unable to discuss their strengths and weaknesses. Many candidates focused on EGDT alone.

Discussion

In response to the Examiner's comment, one might counter by saying that the SSG are so heavily based upon EGDT that a discussion of one is by necessity a discussion of the other. The examiners would counter by pointing out that only 9% of people passed.

It may well be that these candidates in their susceptible state had erroneously conflated this question with Question 16 from the second paper of 2013, having obviously done all the past papers back to front.

A long rambling critique of the EGDT approach is already available elsewhere, and the reader will not be subjected to it here. A distillate of expert opinion regarding the SSG is also available. What follows below is a summary of that summary, hopefully incorporating the important points made in the college model answer.

Advantages of the SSG

High quality of the presented package

• Excellent literature search and summary.
• A good source of literature references
• Produced by an international panel of experts.
• GRADE system makes it easier for clinicians to assess the strength of a recommendation.
• GRADE system separates quality of the evidence from the strength of recommendations.

Evidence in defence of the guidelines

• There is no evidence they do any harm
• Even in Australia patient management seems to be carried out with some awareness of the SSG protocols
• Failure to standardise care may result in an inefficient variation in care.
• Bundled interventions may work synergistically and the whole package may generate greater benefit than the sum of its parts.
• The recommendation for early antibitoics meets high standards for inclusion in protocols.

Criticisms of the SSG

Arguments against bundled care in general:

• All-or-none bundles may promote harmful therapies together with helpful ones.
• Marketing of such bundles may propagate unhelpful therapies.
• There is no evidence that "bundle synergy" exists.
• The quality of care might end up being measured according to bundle compliance.

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.
• GRADE system separates quality of the evidence from the strength of recommendations, which allows one to make strong recommendations on the basis of weak evidence.

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:

• Benefit of SSG implementation is found mainly in"before-and-after" trials, subject to publication bias, patient selection bias, temporal bias, and the Hawthorne effect.
• Frequently only one specific component was independently associated with a treatment effect.
• Often a treatment effect was found in spite of poor compliance with the bundle.

Empirical evidence against the use of the guidelines:

• Sepsis mortality in Australia already began to improve before the first guidelines were published.
• The ProCESS and ARISE studies did not demonstrate any survival benefit from protocolised care.

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.