Elsevier

Journal of Critical Care

Volume 28, Issue 5, October 2013, Pages 756-762
Journal of Critical Care

Clinical Potpourri
Oral midodrine treatment accelerates the liberation of intensive care unit patients from intravenous vasopressor infusions

https://doi.org/10.1016/j.jcrc.2013.05.021Get rights and content

Abstract

Purpose

Persistent low-level hypotension represents a barrier to discharging patients from the intensive care unit (ICU). Midodrine may be an effective adjunct to wean intravenous (IV) vasopressors and permit ICU discharge. We tested the hypothesis that midodrine, given to patients on IV vasopressors who otherwise met ICU discharge criteria, increased the magnitude of change in IV vasopressor rate.

Materials and Methods

This was a prospective, observational study in 20 adult surgical ICU patients who met ICU discharge criteria except for an IV vasopressor requirement. We compared the change in phenylephrine equivalent rates during the day before midodrine to the change in phenylephrine equivalent rates after midodrine initiation and analyzed changes in total body fluid balance, heart rate, mean arterial pressure, and white blood cell count during this period.

Results

Patients received 41.0 ± 33.4 μg/min of phenylephrine equivalents and the change in IV vasopressor rate (slope) decreased significantly from − 0.62 μg/min per hour of phenylephrine equivalents before midodrine to − 2.20 μg/min per hour following the initiation of midodrine treatment (P = .012). Change in total body fluid balance, heart rate, mean arterial pressure, and white blood cell count did not correlate with change in IV vasopressor rate.

Conclusion

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.

Introduction

Persistent hypotension represents a barrier to discharging patients from the intensive care unit (ICU) because intravenous (IV) vasopressors are not typically administered outside of a critical care unit. At our institution, in patients who are otherwise ready for inpatient acute nursing care and monitoring but remain on low rates of IV vasopressors, midodrine has been observed to facilitate weaning of IV vasopressor infusions, thereby promoting ICU discharge. This practice has previously been reported in a case report [1] and two case series [2], [3]; our prospective pharmaco-physiological interaction study was designed to further examine the practice of administering oral vasopressors in the ICU.

Midodrine is an oral α1 agonist with a labeled indication for treatment of symptomatic orthostatic hypotension [4]. Midodrine offers a safer adverse effect profile compared to other oral vasoactive medications. As an α1 agonist, midodrine’s common adverse effects are linked to direct sympathomimetic effects: piloerection [4], [5], [6], [7], shivering [5], paresthesias [4], [5], [6], [7], [8], and urinary retention [4]. Midodrine has been studied in diverse populations including patients with orthostatic hypotension [4], cirrhosis of the liver [9], hepatorenal syndrome [7], dialysis-induced hypotension [10] as well as patients having carotid artery stents placed [3] and immediately following a myocardial infarction [2], and it has generally been well tolerated.

Midodrine is a glycinamide prodrug which undergoes enzymatic hydrolysis to form desglymidodrine. The therapeutic effect of orally administered midodrine is due to this peripherally active alpha-agonist metabolite, desglymidodrine [5]. The plasma level of the prodrug reaches peak blood concentration after about 30 minutes while the active metabolite peaks about 1 to 2 hours after midodrine administration and has a half-life of 3 to 4 hours [6]. Clinically, midodrine produces a predictable response in blood pressure when administered at doses up to 20 mg. In patients with neurogenic orthostatic hypotension, a single 20-mg dose reaches a maximum concentration within 30 minutes and produces a mean increase in standing systolic blood pressure equal to 43 mm Hg after 1 hour [6]. These desirable pharmacological properties lend midodrine to potential application for new indications.

Similar to many off-label treatments used in intensive care units [11], the data supporting the off-label use of midodrine in the ICU is limited. Based on its labeled indication and published case reports, we tested the a priori hypothesis that the magnitude in the decline of IV vasopressor rate is greater during midodrine administration than prior to midodrine treatment.

Section snippets

Study design

This prospective, observational study was performed in the surgical ICU of a tertiary care, academic medical center. Approval for this human study was obtained from the appropriate ethics committee (Partners Institutional Review Board) and implemented in accordance with the ethical standards set in the 1964 Declaration of Helsinki and related amendments. Due to the nature of the study design, Partners Institutional Review Board waived the requirement for patient consent.

Study population

All patients between

Results

Twenty patients met the inclusion criteria and received midodrine therapy during the study period. Nine of the subjects were male and eleven were female. The mean age of the subjects was 65 ± 14 years, the mean APACHE II score was 18 ± 6, the mean Charlson Comorbidity Index was 4 ± 4, and the mean duration of IV vasopressors prior to midodrine initiation was 3 days (IQR, 2-6). The modal dose was 20 mg (range, 5-20 mg) of midodrine three times per day. Baseline demographics and clinical

Discussion

Midodrine significantly increased the magnitude of IV vasopressor decline and, within a single day, assisted in the discontinuation of IV vasopressors in 70% of subjects. Midodrine appears to be the primary reason for the decline in the IV vasopressor rate needed to maintain goal blood pressures.

Prior to the implementation of midodrine, the mean change in phenylephrine equivalent rate was -0.62 μg/min per hour, suggesting that if a subject received 50 μg/min of phenylephrine it would take over

Acknowledgments

The study was completed using departmental funds.

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    Disclosure: The authors state that there is no conflict of interest related to their research on midodrine.

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