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Surviving Sepsis: where the

guidelines went wrong

Jeremy M. Kahn, MD MS

Associate Professor of Critical Care Medicine

Director, Program on Critical Care Health Policy

University of Pittsburgh

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Disclosures

• Grant funding from NIH/HRSA

• Consulting fees from the US

Department of Veterans Affairs

• In-kind research support from Cerner

• No other industry relationships

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Additional notes:

• I won’t be discussing bundles

• I won’t be making any Rob Ford jokes

• I think the guidelines are pretty great

• Had I known RPD and JLV would be up

here, I wouldn’t have agreed to this

talk

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Outline

• Rationale for guidelines

• Review of GRADE

• Some examples and suggestions

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Why do we have guidelines?

• Evidence is complex and voluminous

• Interpreting the evidence is inherently

subjective

Eddy Health Affairs 2007

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Guidelines exist to serve both

steps in this process

• Rate the quality of the evidence

• Make a practice

recommendation based on

– The quality of the evidence

–Preferences and values

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Grading of Recommendations Assessment,

Development and Evaluation (GRADE)

Strength Benefit

Separates evidence

from recs

Flexibility to incorporate values and

preferences, not just evidence

Systematic Specific road-map leads to more

consistent recommendations

Transparent Even if we disagree with the conclusions,

we can see how the conclusion was

reached

Guyatt JCE 2011

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Strength of evidenceStudy Design Quality of Evidence Lower if Higher if

Randomized trial High (A) Risk of bias: Large effect:

-1 Serious +1 Large

-2 Very serious +2 Very large

Moderate (B) Inconsistency Dose response

-1 Serious +1 Evidence of a gradient

-2 Very serious

All plausible confounding

Indirectness + 1 Would reduce a

Observational study Low (C) -1 Serious demonstrated effected or

-2 Very serious

+1 Would suggest a

Imprecision spurious effect when

-1 Serious results show no effect

Very low (D) -2 Very serious

Publication bias

-1 Likely

-2 Very likely

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Strength of recommendation

Factors

Quality of evidence

Balance between desirable and undesirable effects

Importance of the outcome

Costs (resources allocation)

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Result of a GRADE evaluation

• Strength of recommendation

– Strong (1-“We recommend”)

– Weak (2- “We suggest”)

• Quality of evidence

– High (A)

– Moderate (B)

– Low (C)

– Very low (D)

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Dellinger CCM 2012

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Two potential missteps

• Fluid management in ARDS

• Stress ulcer prophylaxis in

mechanical ventilation

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Fluid management in ARDS

• “We recommend a conservative fluid

strategy for patients with established

sepsis-induced ARDS who do not have

evidence of tissue perfusion (1C)”

– Strong recommendation based on low

quality evidence

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• Directness: only 25% had sepsis

• Patient-centeredness:

– No impact on mortality

– 2.5 additional VFDs

• Relative burden

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Impaired Not impaired P value Adjusted OR

PaO2 86 71 0.021.51

(1.01 – 2.26)

Conservative

fluid strategy32% 66% 0.004

3.35

(1.16 – 9.70)

Mikkelsen AJRCCM 2012

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Stress ulcer prophylaxis

• “We recommend that stress ulcer

prophylaxis be given to patients with

severe septic shock who have

bleeding risk factors (1B)”

– Strong recommendation based on high

quality evidence

– PPIs > H2 blockers (2C)

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Evidence

• Cited studies:

– do not compare prophylaxis to no

prophylaxis

– do not post-date 1986

• Meta-analyses do not report patient-

centered endpoints

• Potential harm

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• No effect on mortality

• Higher mortality in patients who are

enterally fed and received H2

blockers

Marik Crit Care Med 2010

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Herzig JAMA 2009; Howell Archives 2010

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Strong recommendations

• Just do it

• If giving the choice, nearly all patients

would want the therapy

• Rarely base on low quality evidence

Is that the case here?

Guyatt BMJ 2008

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GRADE to the rescue

• Guideline committee:

– Considered GI bleeding to be morbid and

worthy of prevention

– Did not find evidence of harm convincing

• Subjective but transparent

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Just 2 examples, but…

• Of 83 adult recommendations, 13

(16%) are strong recs based on low

quality evidence

1A/B

1C/D2 A/B

2 C/D

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Unintended consequences

• Stress ulcer prophylaxis as a quality

measure (just do it!)

• Decreases trustworthiness of the rest of

the guideline

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Conclusions

• The Surviving Sepsis Guidelines are an

impressive undertaking that are likely

to improve sepsis care

• Guideline developers both smart and

handsome

• But

– Too many recommendations

– Too many 1 C/D recommendations

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www.ccm.pitt.edu/crisma