Landmark Papers in Critical Care: vasopressin vs norepinephrine for septic shock

Septic shock is often called “warm shock” because despite poor O2 delivery, the blood vessels are dilated. Vasopressin, which is a vasoconstrictive peptide, is relatively deficient in septic shock. Sometimes it is added on to other pressors in patients with severe septic shock. Could vasopressin be the best pressor for septic shock?  The VASST trial aimed to find out.

This 2008 trial looked at how patients in septic shock did on IV vasopressin compared to norepinephrine. The patients enrolled were hypotensive despite adequate fluid resuscitation and at least 5 mcg/min of norepi for 6 hrs or 15 mcg/min for 3 hrs. Patients were randomized to either vasopressin (starting at 0.01 units/min and titrated to 0.03 units/min over 40 min) or NE (starting at 5 mcg/min and titrated up to 15 mcg/min over 40 min). After 28 days there was no significant difference in mortality. However, subgroup analysis showed that there WAS a significant mortality benefit for vasopressin in patients who initially had lower pressor requirements…huh?

This was a little confusing to reviewers and the authors themselves, which is why in the accompanying editorial, it was suggested that these findings are not definitive for management of sepsis, but are rather, “hypothesis-generating.” The editorial goes on to point out that other studies have shown that time to pressors is probably more important than which pressor is chosen.


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