In this episode, I’ll discuss the use of adjuvant midodrine in patients with septic shock.
Using midodrine to wean ICU patients off of vasopressors is a common strategy and one that I have used in my practice and discussed in previous episodes.
The general principle is that some ICU patients seem otherwise medically stable, yet cannot completely wean off of their vasopressor without episodes of hypotension. This delays their stay in the ICU when they would otherwise be eligible for transfer to a lower level of care. If midodrine can be used to wean a patient off an IV vasopressor, then the patient could be transferred out of the ICU, reducing length of stay and possibly other ICU-related complications up to and including mortality.
Study results on using midodrine in patients with septic shock for this purpose have been mixed, but a recent meta-analysis suggested the additional use of midodrine might reduce hospital mortality and ICU mortality in patients with septic shock.
A group of authors sought to investigate what would happen to patients with septic shock if, instead of waiting until it was time to wean norepinephrine, they started midodrine at the same time as norepinephrine in an adjuvant fashion. To attempt to prove that the adjuvant use of midodrine could reduce vasopressor use and decrease length of stay in patients with septic shock, the authors published a randomized controlled trial in Pharmacotherapy.
One hundred patients with septic shock were randomized to either the control group, who received intravenous norepinephrine, or the midodrine group, who received intravenous norepinephrine and enteral midodrine 10 mg every 8 h.
The primary outcome was 28-day in-hospital mortality, and secondary outcomes included 7-day ICU mortality, the average dose of norepinephrine, the duration of intravenous norepinephrine, ICU length of stay, and in-hospital length of stay.
The 28-day mortality rate was numerically lower in the midodrine group vs control at 54% vs 68%. However, the 95% confidence interval suggested the risk difference could be anywhere from 32% in favor of midorine to 5% in favor of control, and so the difference was not statistically significant.
The 7-day ICU mortality rate findings were nearly identical to the 28-day mortality findings, numerically in favor of midodrine but not statistically significant.
The average IV norepinephrine dose in the midodrine group was significantly lower compared to the control group. Unfortunately, this did not translate to a significant difference in the duration of IV norepinephrine use. As one would expect with no effect on norepinephrine duration, midodrine also did not favorably impact ICU or hospital length of stay.
The authors concluded:
The findings did not demonstrate a significant reduction in mortality with adjuvant midodrine use in the treatment of septic shock. Midodrine appears to reduce the need for vasopressors. However, our findings did not support that midodrine shortens the duration of vasopressor use nor the course of hospitalization for patients with septic shock.
This trial is important because previous studies of midodrine did not focus on adjuvant use in patients with septic shock. There is still room for more research in this area, particularly with using different dosage schemes for midodrine – either increasing the dose per administration or giving it more frequently. Until more research is available, it doesn’t seem like routine adjuvant use of midodrine in patients with septic shock is supported.
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.
If you like this post, check out my book – A Pharmacist’s Guide to Inpatient Medical Emergencies: How to respond to code blue, rapid response calls, and other medical emergencies.
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