In this episode, I will discuss the use of midodrine to wean ICU patients off of vasopressor infusions.

At the time of this episode, I am hosting a closed beta program for my Critical Care Pharmacy Academy, a private, paid membership group where I teach other pharmacists about critical care.

I plan to open the Academy for others to join in December 2016.

The Academy includes ‘masterclass’ lectures that cover critical care topics in-depth. So far I have recorded lectures on ICU Rounds, Patient Assessment, and Airway Pharmacology.

If you want to know more about this when it opens you can sign up to be notified at pharmacyjoe.com/academy.

The complications of prolonged ICU stay are well known and include delirium, infection, immobility, and excessive cost. Occasionally, critically ill patients recover from their illness but have difficultly weaning off of IV vasopressors. Continued use of IV vasopressors delays discharge from the ICU.

Midodrine

Midodrine is an oral administered prodrug of desglymidodrine, an alpha-1 receptor agonist. Midodrine increases blood pressure by increasing arteriolar and venous tone.

In an otherwise stable patient on low amounts of IV vasopressors, midodrine has the potential to replace the need for IV vasopressors and allow for transfer out of the ICU.

Studies

Several small studies seem to confirm the logical conclusion that oral midodrine can allow for faster weaning of IV vasopressors and ICU discharge in select patients.

In 2013, a prospective, observational study in 20 adult surgical ICU patients concluded:

Midodrine treatment was associated with an increase in the magnitude of decline of the IV vasopressor rate. Oral midodrine may facilitate liberation of surgical ICU patients from an IV vasopressor infusion, and this may affect discharge readiness of patients from the ICU.

In 2016 a retrospective study of 275 patients with septic shock from a single center reported:

Mean IV vasopressor duration was 3.8 days in the IV vasopressor only group and 2.9 days in the IV vasopressor with midodrine group (P < .001). …ICU length of stay was 9.4 days in the IV vasopressor only group and 7.5 days in the IV vasopressor with midodrine group (P = .017).

In 2016 a retrospective study of 188 patients from a single center reported:

Patients discontinued IV vasopressors a median of 1.2 days after midodrine initiation. ICU discharge occurred sooner after IV vasopressor discontinuation (0.8 vs. .15 days, P = 0.01), and 96% of patients remained off IV vasopressors after midodrine treatment. Hospital LOS was longer in midodrine patients (P < .001), but there were no differences in ICU LOS or readmissions. Adverse event rates after midodrine use were consistent with those observed in other studies.

Unanswered questions

Based on these retrospective studies, midodrine is associated with a decreased length of stay in the ICU. However, it is wishful thinking to assume that this translates to any clinically meaningful patient outcome. The ideal dose, tapering schedule, and safety profile remain questions without high-quality answers.

Several institutions report they initiate midodrine at a dose of 20 mg orally every 8 hours when attempting to wean patients off of vasopressors. The midodrine dose is increased by 10 mg per dose each day until the vasopressors can be weaned or a maximum dose of 40 mg every 8 hours is reached. It may be reasonable to reduce these doses in the setting of renal failure.

I’ve yet to see any study of midodrine for weaning IV vasopressors that include a description of a tapering schedule. Due to the 3-4 hour half-life of midodrine, it can likely be tapered off quickly. However, the decision to taper would likely be made in a general medical unit – where there is less ability to closely monitor a patient’s response to a reduction in midodrine dosage.

Safety data for using midodrine to taper off IV vasopressors is sparse. Some studies look at ICU readmission rates and general adverse effect rates. But clinically meaningful outcomes such as changes in morbidity and mortality have not been examined.

Ongoing trial

Researchers at Massachusetts General Hospital have a prospective, double-blind, randomized trial underway of midodrine vs placebo for the treatment of refractory hypotension in patients otherwise ready for discharge from the ICU. Outcome measures include:

Time until discontinuation of IV vasopressors (Primary outcome)

ICU length of stay

Hospital length of stay

Rates of ICU readmission

Rates of hypertension, bradycardia, and hemodynamically significant tachyarrhythmias

The estimated study completion date is August 2016 however it is still listed as “currently recruiting participants” according to clinicaltrials.gov.

Conclusion

While the practice of using midodrine to facilitate weaning from IV vasopressors is apparently effective, I’ll be keeping a close eye on future studies to get a better idea of the safety and dosing aspects of using midodrine for this indication.

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