ICU discharge is often delayed by a requirement for intravenous vasopressor medications to maintain normotension. We hypothesised that the administration of midodrine, an oral α1-adrenergic agonist, as adjunct to standard treatment shortens the duration of intravenous vasopressor requirement.
In this multicentre, randomised, controlled trial including three tertiary referral hospitals in the US and Australia, we enrolled adult patients with hypotension requiring a single-agent intravenous vasopressor for ≥ 24 h. Subjects received oral midodrine (20 mg) or placebo every 8 h in addition to standard care until cessation of intravenous vasopressors, ICU discharge, or occurrence of adverse events. The primary outcome was time to vasopressor discontinuation. Secondary outcomes included time to ICU discharge readiness, ICU and hospital lengths of stay, and ICU readmission rates.
Between October 2012 and June 2019, 136 participants were randomised, of whom 132 received the allocated intervention and were included in the analysis (modified intention-to-treat approach). Time to vasopressor discontinuation was not different between midodrine and placebo groups (median [IQR], 23.5 [10–54] vs 22.5 [10.4–40] h; difference, 1 h; 95% CI − 10.4 to 12.3 h; p = 0.62). No differences in secondary endpoints were observed. Bradycardia occurred more often after midodrine administration (5 [7.6%] vs 0 [0%], p = 0.02).
Midodrine did not accelerate liberation from intravenous vasopressors and was not effective for the treatment of hypotension in critically ill patients.
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De-identified data collected during the trial will be made available upon reasonable request to researchers who provide a methodologically sound proposal, after approval by the study authors, and with a signed data access agreement. Questions about data are handled by the corresponding author.
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The members of the MIDAS study group are Peter Santer, Matthew H. Anstey, Maria D. Patrocínio, Bradley Wibrow, Bijan Teja, Denys Shay, Shahzad Shaefi, Charles S. Parsons, Timothy T. Houle, Matthias Eikermann, Kwok M. Ho, Stefan J. Schaller, Tharusan Thevathasan, Lea Albrecht, Stephanie Grabitz, Khushi Chhangani, Pauline Y. Ng, Alexander Levine, Alan DiBiasio, Robert Palmer, Erina Myers, Rashmi Rauniyar, Todd Sarge, Flora Scheffenbichler, and Alok Gupta.
This study was in part funded by philanthropic donations from Jeffrey and Judy Buzen to Matthias Eikermann: funds were allotted to support time and effort of study personnel. The funders had no role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and the decision to submit the manuscript for publication.
Conflicts of interest
Matthias Eikermann has received unrestricted funds from philanthropic donors Jeffrey and Judy Buzen and grants from Merck & Co. outside of the submitted work. All other authors declare no conflicts of interest.
This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the local institutional review boards at Massachusetts General Hospital (Partners Human Research Committee, #2016P002045), Sir Charles Gairdner Hospital (Sir Charles Gairdner Hospital HREC, #2015-098), and Beth Israel Deaconess Medical Center (Committee on Clinical Investigations, #2018P000162).
Written informed consent was obtained from all subjects or their legally authorised representatives.
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The members of the MIDAS study group are listed in “Acknowledgements”.
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Santer, P., Anstey, M.H., Patrocínio, M.D. et al. Effect of midodrine versus placebo on time to vasopressor discontinuation in patients with persistent hypotension in the intensive care unit (MIDAS): an international randomised clinical trial. Intensive Care Med 46, 1884–1893 (2020). https://doi.org/10.1007/s00134-020-06216-x
- Oral vasopressor
- Persistent hypotension
- ICU discharge