Thursday, December 31, 2009

Top 10 issues in hospital medicine for 2009, issue 4: controversies in sepsis management

This comes up every year and 2009 was no exception. Despite new developments and continued attacks on the Surviving Sepsis Campaign the guidelines, I believe, are still reliable. Here's what caught my attention this year:

Early goal directed therapy

A meta-analysis confirmed that early, but not late, goal directed therapy works.

Despite public controversy about EGDT evidence continues to mount in favor of the protocol and the pathophysiologic rationale is compelling. EGDT is a package of interventions, and one of the controversies is whether the entire package is necessary or whether some component interventions can be eliminated. That question is the subject of a NIH trial just getting underway.

A Bayesian analysis was critical of EGDT but did not take into account the appropriate prior evidence.

Lactate levels

Point of care measurement in the ER is useful.

Choice of pressor agent

Although evidence tends to favor norepinephrine the issue remains controversial, and optimal use requires taking into account the individual patient's hemodynamic status. I cited a new paper and a helpful topic review here.

Activated protein C

Although this agent remains controversial I didn't find a lot that was new in 2009. There was one interesting paper about the appropriateness of the product labeling, pointing out that the contraindications do not include all the patient exclusion criteria in PROWESS. If the exclusions in PROWESS (which encompass both the contraindications and the “warnings and precautions” in the labeling) are followed in clinical use the drug seems to perform better from a safety standpoint.

Glycemic control

After mounting negative evidence concerning intensive glycemic control in critical illness this year saw publication of NICE-SUGAR which failed to show benefit. What do we know at the end of 2009? We know we shouldn't ignore the blood glucose in septic patients but we don't know the optimal target. An editorial put it this way:

Despite these caveats, we think it is important to emphasize that the findings of NICE-SUGAR do not justify neglecting glycemic control. Instead, we think that, whatever the mechanisms behind the findings of NICE-SUGAR, there is now a new and more moderate standard of care for glycemic management in the ICU: do not treat hyperglycemia unless the glucose level increases higher than 180 mg/dL; when you do treat hyperglycemia, aim for a target blood glucose concentration between 144 and 180 mg/dL. Until a study can provide level I evidence that a better approach exists, this should remain the standard of care. Such a standard of care also implies that, for example, in patients in the ICU, a glucose level of 243 mg/dL is just as undesirable as a glucose level of 80 mg/dL.


Did CORTICUS, published almost two years ago, close the book on this controversy? Far from it. A systematic review published this year may have swung the pendulum back just a bit. What's really going on? Critical illness related corticosteroid insufficiency (CIRCI) is a real entity. What's more, occasional patients with sepsis may have full blown adrenal insufficiency resembling classic Addisonism. When all is said and done the current guideline recommendation that corticosteroids be reserved for patients who are refractory to pressors seems reasonable. Clinical judgment, however, may dictate other approaches in individual patients. I posted on this topic last July.

General reviews

I found these this year: [1] [2]

Initial antibiotic therapy

Growing evidence shows that covering the spectrum adequately, and doing it early, are important.

Surviving Sepsis Campaign

Promotion of the Surviving Sepsis Guidelines increased adherence and saved lives. This is the first study ever done, as far as I know, on the effect of pharmaceutical industry promotion on hard clinical outcomes.

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