Clinical PotpourriOral midodrine treatment accelerates the liberation of intensive care unit patients from intravenous vasopressor infusions☆
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.
References (22)
- et al.
Neurogenic orthostatic hypotension: a double-blind, placebo-controlled study with midodrine
Am J Med
(1993) - et al.
Effects of a 7-day treatment with midodrine in non-azotemic cirrhotic patients with and without ascites
J Hepatol
(2007) - et al.
Off-label medication use in adult critical care patients
J Crit Care
(2011) - et al.
Midodrine improves chronic hypotension in hemodialysis patients
Am J Med Sci
(2003) - et al.
Early mobilization in critically ill patients: patients' mobilization level depends on health care provider's profession
PM R
(2011) - et al.
Midodrine, an alternative to intravenous vasopressor therapy after spinal surgery
Eur J Anaesthesiol
(2002) - et al.
Successful treatment of hypotension associated with stunned myocardium with oral midodrine therapy
J Cardiovasc Pharmacol Ther
(2005) - et al.
Oral midodrine is effective for the treatment of hypotension associated with carotid artery stenting
J Cardiovasc Pharmacol Ther
(2008) - et al.
Efficacy of midodrine vs placebo in neurogenic orthostatic hypotension. A randomized, double-blind multicenter study. Midodrine Study Group
JAMA
(1997) - et al.
Pharmacodynamics of midodrine, an antihypotensive agent
Clin Pharmacol Ther
(1986)
A double-blind, dose-response study of midodrine in neurogenic orthostatic hypotension
Neurology
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2022, Journal of Critical CareA pilot, feasibility, randomised controlled trial of midodrine as adjunctive vasopressor for low-dose vasopressor-dependent hypotension in intensive care patients: The MAVERIC study
2022, Journal of Critical CareCitation Excerpt :The practical study design was feasible to answer our stated hypothesis. Midodrine has previously been evaluated for a variety of off-label clinical indications relevant to critical care, including weaning off intravenous vasopressors [5-10], prevention of complications in cirrhotic patients [16], as a substitute for albumin in abdominal paracentesis-related hypotension [17] and in post-operative settings for carotid artery stenting [18] and spinal surgery [19]. Similar to our study, significant adverse effects were uncommon.
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2020, Journal of Critical CareCitation Excerpt :Of the observation studies evaluated, a majority of the studies found a statistically significant benefit with the use of midodrine on accelerating weaning and/or discontinuation of IV catecholamine vasopressors [8,9]. A study by Levine et al. found that in 20 patients, midodrine use allowed for a more rapid weaning of IV vasopressors [8]. Prior to midodrine use, IV vasopressors were weaned at a rate of 0.62 ± 1.40 μg of phenylephrine equivalents/min every hour; however, after 4 doses of midodrine, the IV vasopressors were able to be weaned at a rate of 2.20 ± 2.45 μg/min per hour (p = .01).
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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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