In this episode, I’ll discuss the use of dexmedetomidine to reduce vasopressor resistance in refractory septic shock.
Subgroup and post-hoc trial analysis has hinted at dexmedetomidine having a surprising effect on enhancing vasopressor responsiveness in refractory septic shock patients. While this sounds paradoxical given that hypotension is a common side effect of dexmedetomidine, the theory to explain the previous study findings is that sympathetic hyperactivation is responsible for decreased vasopressor sensitivity, and the effects of dexmedetomidine may reverse this.
To test this theory, a group of authors have published in the journal Critical Care Medicine a randomized controlled pilot study looking at Dexmedetomidine to Reduce Vasopressor Resistance in Refractory Septic Shock. The study enrolled 32 patients who had septic shock and a norepinephrine requirement greater than or equal to 0.25 µg/kg/min with persistent circulatory failure, which was defined as lactate > 2 mmol/L, oliguria, or skin mottling. All patients also required invasive mechanical ventilation.
The authors measured each patient’s arterial pressure response to phenylephrine before starting the treatment and at 6 and 12 hours. In the treatment arm, dexmedetomidine was given at a fixed dose of 1 µg/kg/hr.
Unfortunately, enrollment was stopped early because of higher mortality in the dexmedetomidine arm. Response to phenylephrine was significantly lower in the dexmedetomidine arm than placebo at 6 hours, although this difference was also significant at baseline. Mortality on day 3 was higher in the dexmedetomidine group compared to placebo; however, this difference was no longer significant by day 30.
The authors concluded:
Patients in the dexmedetomidine arm had a significantly lower response to phenylephrine at all study times including baseline, which might have contributed to higher early mortality in the dexmedetomidine arm and preclude to conclude on dexmedetomidine efficacy in refractory septic shock. However, heart rate was not decreased in the dexmedetomidine arm.
Because of the difference existing at baseline, the journal editors point out that the results of this study do not allow any conclusions on dexmedetomidine efficacy to alleviate vasopressor resistance in refractory septic shock patients. However it would be prudent to not use dexmedetomidine specifically for this purpose until a better study without significant baseline differences between groups can be performed.
The article in this episode is a selection from my Hospital Pharmacy Academy’s weekly literature digest. Have you ever felt like your physician colleagues are one step ahead of you with new literature developments? Every week, Academy members are provided a summary curated and explained by me of the top hospital pharmacy-related articles published that week from over 20 major journals and sources to save you time and keep you up to date with the literature. To get immediate access, go to pharmacyjoe.com/academy.
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