Monday, October 23, 2006

The Surviving Sepsis Campaign guidelines: evidence based or not???

An exhaustive review on sepsis in the October 19 issue of the New England Journal of Medicine (NEJM) covers nomenclature, pathophysiology and treatment, including a discussion of the Surviving Sepsis Campaign guidelines. But in what could be viewed as a strange attempt on the part of the Journal to appear “fair and balanced” the same issue’s Perspective piece entitled Surviving Sepsis---Practice Guidelines, Marketing Campaigns, and Eli Lilly dismisses the guidelines as little more than a marketing strategy disguised as evidence based medicine. The authors base their criticism entirely on the role of Eli Lilly in the development and promotion of the guidelines, which endorse its drug Xigris (activated protein C) for restricted indications in patients with severe sepsis. (When I wrote about this controversy 5 months ago I took the more moderate position that the Eli Lilly ties deserved exposure and these guidelines, like any guidelines should be viewed with healthy skepticism. I also took the position that any responsible criticism of the guidelines should appeal to the primary sources of evidence and not be based solely on arguments concerning industry affiliation).

Guidelines, though useful, are imperfect. This can have unintended consequences when they are promulgated by agencies like IHI and JCAHO or become the focus of pay-for-performance initiatives. Even greater harm can result when they are hijacked by the trial lawyers and their hired guns under the rubric of “standard of care.”

Although the authors correctly point this out their criticism of the sepsis guidelines is misdirected and at times defies logic. Proper criticism of the guidelines should be based on the measuring stick of evidence. Portions of the Surviving Sepsis Guidelines indeed depart from high level evidence. The Perspective piece authors, however, don’t seem to care about evidence and disregard the fact that the only examples of the guidelines’ departure from evidence are unrelated to influence by Eli Lilly.

So let’s look at how each recommendation in the guidelines stacks up:

Early goal directed therapy----supported by high level evidence.
Diagnostic studies to ascertain source and microbiology---supported by low level evidence.*
Antibiotic therapy---supported by low level evidence.*
Source control---supported by low level evidence.*
Fluid therapy recommendations---supported by low level evidence.
Vasopressor recommendations---supported by low level evidence.
Inotropic agents---supported by low level evidence (high level evidence if used as part of early goal directed therapy).
Corticosteroids---conflicting evidence; use is controversial.
Activated protein C---supported by high level evidence.
Low tidal volumes for patients requiring mechanical ventilation---supported by high level evidence.
Sedation protocols and avoidance of neuromuscular blocking agents in mechanically ventilated patients---supported by high level evidence.
Intensive glycemic control---not supported.
Renal replacement therapy recommendations---supported by high level evidence.
Non-recommendation of bicarbonate therapy for most cases of hypoxic lactic acidosis---supported.
DVT prophylaxis---supported by high level evidence.
Stress ulcer prophylaxis---supported by high level evidence.

*Although diagnostic studies, antibiotic therapy and source control recommendations are based on “weak” evidence the guideline authors unequivocally recommend these measures. The ethical problems in demanding high level evidence for these modalities are obvious.

From the synopsis above it is readily apparent that any evidence based criticism of the Surviving Sepsis Guidelines would have to question intensive glucose control and the use of corticosteroids. The Perspective authors were conspicuously silent about these, the two weakest recommendations in the document. Why? Because they can’t blame it on the drug companies! Cheap, generic, plain ole insulin and hydrocortisone, the only non-evidence based drugs supported by the guidelines, are of no financial interest to the drug companies.

Gotta ask this question: is this ad hominem attack on the sepsis guidelines anything more than gratuitous bashing of the drug companies?


Daniel Haszard said...

Eli Lilly 3Q 10% profit rise is nearly all from psyche drugs including zyprexa.How have they schemed to squeeze more money from their zyprexa cash cow when pill production has actually gone down?

ANS-Eli Lilly profiteers have jacked up the price of zyprexa to the federal govt,from the Medicare D payouts.Eli Lilly is a big drug company that puts profits over patients.

They covered up findings that their Zyprexa has a TEN times greater risk of causing type 2 diabetes

Only 9% of Americans trust big pharma,right around the same rating as tobacco companies.

Daniel Haszard Eli Lilly zyprexa drug caused my diabetes

Anonymous said...

I do agree that pahrmaceutical companies play too large a role in modern day medicine. It's disgusting to see physicians paid by pharma to "teach" other physicians. Corruption disguised bin a "guideline" or covered up ina a white coat is...corruption.

Anonymous said...

Please see an audio reply by Dr. Levy from SCCM at