UMEM Educational Pearls

It is a common scenario in the ICU, and occasionally in the ED, to be asked which pressor you would like to wean first, norepinephrine or vasopressin.  This is mostly an “art not science” question, but is there a right answer?  Does picking one vs the other to wean first lead to less hypotension?

Bottom Line: This meta-analysis doesn't suggest that either the norepi-first or vasopressin-first strategies for vasopressor wean are associated with an increased incidence of hypotension, although the literature is mixed.  Whatever your current practice is, it's probably reasonable to stick with that.  See the additional information for my personal approach.

Additional Information

This meta-analysis looked at both observational studies and RCTs.  Interestingly, the observational studies suggested, with statistical significance, that weaning norepi first was associated with more hypotension, but the RCTs suggested the opposite (that weaning norepi first was associated with less hypotension).  When put together, the literature overall doesn't suggest a difference.  It remains unclear whether it's better to wean the norepinerphine first or vasopressin first.  

My personal practice is to:

1. Review the vital signs and other data to attempt to ascertain to what degree the patient was a vasopressin responder.  Did their BP increase significantly after vaso was started?  Do they have conditions which suggest they may be vasopressin deficient (e.g. cirrhosis, central DI, older age, prolonged sepsis)?  If I think the vaso is a large part of why their BP improved, I may opt to wean it last.  If I feel their response to vaso was limited and/or they're unlikely to be vasopressin deficient, I may opt to wean it first.
2. To what degree is the patient's BP marginal vs solid?  Keep in mind, in most units (including ours) the practice is to manage vasopressin as simply on/off, and not titrate by degrees.  So if their MAP is 66 and my goal is 65, turning the vaso totally off may cause problems.  In that case I may focus on the norepi (or go ahead and turn the vasopressin off but tell the nurse they can go up on the norepi if needed, depending on what my current norepi dose is).  But if their BP is more robust and they have some runway, especially if per #1 they don't seem too dependent on the vaso, I'm more inclined to go ahead and turn off the vaso.
3. Is there some other reason I really like vasopressin in this patient?  The primary use case tends to be right heart dysfunction, as the lack of V1 receptors on the pulmonary vasculature mean vaso (unlike norepi/epi) increases SVR without increasing PVR.  I may be more interested in weaning the norepinephrine first if the patient has right heart issues (e.g. PE, pulmonary hypertension, decompensated RV failure).  It's also a (minor) consideration if they have an element of diabetes insipidus or hypernatremia and we're looking to control their sodium or urine output.  But that's a very minimal thought, as pressor-dose vasopressin doesn't impact electrolytes that much.
4. All else being equal, as mentioned in #2, norepineprhine is usually titratable and vasopressin is usually not, plus vasopressin tends (in the US anyways) to be more expensive.  So if I'm truly ambivalent, I'll usually turn off the vasopressin first, and then attend to the norepinephrine.

References

Mallmann C, Silva LOJ, Oliveira MS, Galiotto TMB, Nedel WL, Moraes RB. Effect of norepinephrine versus vasopressin weaning on incidence of hypotension in septic shock patients: a systematic review and meta-analysis. Crit Care Sci. 2026 Feb 16;38:e20260197. doi: 10.62675/2965-2774.20260197. PMID: 41711789.

Effect of norepinephrine versus vasopressin weaning on incidence of hypotension in septic shock patients: a systematic review and meta-analysis - Search