Do You Titrate Vasopressin?

Compared to catecholamine infusions which are routinely titrated, there’s a polarized practice with vasopressin – those who titrate and those who don’t. As a resident, I worked with intensivists who strongly believed in “0.04 U/min or nothing at all.” They believed that similar to electrolyte repletion, vasopressin at this fixed dose (used in many studies) addressed a deficiency in the critically ill population beyond which there was no additional benefit. Torbic et al. showed that even adjusting vasopressin for weight/BMI in septic shock did not change MAP or concurrent catecholamine infusion doses. So maybe a fixed dose is enough? 

Transitioning to a different medical center, I saw more cardiac anesthesiologists and intensivists titrating vasopressin anywhere from 0.01 to 0.10 units/minute. There are plenty of vasopressin titration protocols one can look up online and which have also been used in studies to achieve a mean arterial pressure goal. I’ve also bolused vasopressin after coming off cardiopulmonary bypass and in trauma with associated acidosis with very good results. But are higher doses safe?

I can’t find any studies directly addressing the question of fixed dose versus titrated vasopressin. Intuitively, one would think that a higher dose (0.10 U/min) would activate more V1 receptors causing more vasoconstriction. But could this, in turn, cause more ill effects like digital ischemia?

What do you all do at your respective institutions? Is there literature in favor of a specific practice? Drop me a comment with your experiences!

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  1. The notion of high dose vasopressin being risky and the 0.04 standard came from a pilot retrospective study for the vaast study. The data was from the 90’s and isn’t generalizable to modern standard of care. In all likelihood, the morbidity/mortality wasn’t related to vasopressin at all and was due to the high baseline mortality expected in the study. There is also reasonable data that shows digital ischemia is more closely correlated to underlying physiology that requires high dose pressors than to the high dose pressors themselves.

    As for titration, I work in medical, surgical, and cardiac icu’s. We will titrate up to 0.08 with no unexpected ill effects observed and routinely see a response to titration. So much so that it is a part of my education to fellows and residents that quote literature saying it doesn’t happen. They are stunned to see it work. I usually champion evidence based practices, however I’ve seen too many people respond to titration to accept the data that refutes it.

    • I’m inclined to agree, Mark! I started off with fixed-dose practices but then routinely titrated vasopressin in my last fellowship with success. Thanks for sharing your insight!

    • If i recall the study correctly, the pt was already on a crap ton dose of norepi anyways… I believe the idea of 0.04 u/min came from some guy from Columbia (NYC, not the country) that did some study back in the day and somehow determined that the post pituitary produces 48 units equivalent per day. If you do the math that’s 0.04 u/min.

      But this idea is wildly unscientific anyways. 0.04u/min isn’t even weight-based. 0.04 u/min for a 50kg lady and a 100kg male are very different doses. The idea also doesn’t take into account the idea of baseline vaso-tone. If someone is already in a low SVR state (e.g. cirrhotics) then 0.04 u/min might be homeopathic dose. There are some ridiculous dosing in the hepatology literature.

      • Excellent points! Intuitively, it’s always dangerous to do fixed-dose-anything in medicine for the reasons you mentioned (weight, underlying pathophysiology, etc.) I find myself titrating to effect these days.

  2. Currently I work on the cardiac thoracic unit institution in New York, vasopressin is often used on the unit. The drug is titrated to a max dose of 0.04 units/min and not above. the evidence to support titration above this dosage is very little as most Physicians may share your view on the activation of more V1 receptors caused more vast construction.. At a dose of 0.04 units/min over a period of time patient are at risk for digital ischemia have seen it first hand..


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