Case 1 concluded – norepinephrine reigns supreme?

The poll results are in.. although a small sample size, 100% of respondents would use norepinephrine as their first pressor in septic shock. Let’s take a look at the evidence that may support this stance.

Before a full evidence review, it may be useful to review the basic physiology of pressors and inotropes. Chris Overgaard’s review in Circulation 2008, available open-access, is a great resource to review the basic science behind these medications.

Turning to the evidence, a number of trials have compared agents head-to-head including norepinephrine, dopamine, vasopressin, phenylephrine, and epinephrine. A 2011 Cochrane Review found that these trials have not found any significant differences in hard outcomes of mortality, ICU length of stay, or hospital length of stay, But a few nuances have been revealed..

When specifically comparing norepinephrine and dopamine, this meta-analysis in 2012 showed superiority of norepinephrine with regards to mortality (48 vs 53%) as well as being less arrythmia-inducing (RR 0.43). The bulk of patients in this analysis are from the SOAP II trial.

It’s this body of evidence that provides the background for the 2012 Surviving Sepsis Campaign Guidelines recommendation that norepinephrine be the first choice vasopressor.

The last point I want to briefly touch upon is the role of vasopressin as an adjunct to norepinephrine in septic shock. The VASST trial (NEJM 2008) compared patients with septic shock already on norepineprhine to either higher doses of norepinephrine or adding vasopressin. No difference was found in mortality or adverse events. When looking at the predefined subgroup of less severe sepsis (on 5-14 mcg/min of norepinephrine), mortality was lower in the vasopressin group (26 vs 36%). The approach of adding vasopressin to norepinephrine is supported in the 2012 Surviving Sepsis Campaign.

Thanks again for following, and stay tuned for more cases and pearls!

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