ORIGINAL ARTICLE Effects of Midodrine Hydrochloride on Blood Pressure Cerebral Blood Flow During Orthostasis in Persons Wi Chronic Tetraplegia Jill M.Wecht, EdD,Dwindally Rosado-Rivera, EdD,John P. Handrakis, PT,EdD,Miroslav Radulovic, MD, William A. Bauman, MD ABSTRACT.WechtJM, Rosado-Rivera D, Handrakis JP, Radulovic M, Bauman WA. Effects of midodrine hydrochlo- ride on blood pressure and cerebral blood flow during ortho- stasisin personswith chronic tetraplegia. Arch PhysMed Rehabil 2010;91:1429-35. Objective: To determine the mean arterial pressure (MAP) and middle cerebral artery mean blood flow velocity (MFV) responses to 5 and 10mg midodrine during head-up tilt (HUT) in persons with tetraplegia. Design: Prospective dose-response trial. Setting: James J. Peters Veterans Administration Medical Center. Participants: Persons (N⫽10) with chronic tetraplegia (du- ration of injury⫽23⫽11y). Intervention: A dose titration study was performed over 3 testing days: control (no drug), 5mg midodrine (5mg), or 10mg midodrine (10mg) during 30 minutes of baseline (predrug/no drug), 30 minutes of supine rest postdrug/no drug, 15 minutes of progressive HUT (5 minutes at 15°,25°, 35°),and 45 minutes of 45° HUT. Main Outcome Measures: MAP and MFV response to midodrine supine and during HUT. Results: Tenmilligramsofmidodrinesignificantly in- creased MAP while supine and during the HUT maneuver. Of note, the mean increase in MAP during HUT with 10mg was a result of a robust effect in 2 persons, with minimal change in the remaining 8 study subjects. The reduction in cerebral MFV during HUT was attenuated with 10mg. Conclusions: These findings suggest thatmidodrine 10mg may be efficacious for treatment of hypotension and orthostatic hypotension in select persons with tetraplegia. Although mido- drine is routinely prescribed to treat orthostatic hypotension, the results of our work suggests limited efficacy of this agent, but additional studies in a larger sample of subjects with spinal cord injury should be performed. Key Words: Hypotension, orthostatic; Midodrine; Rehabi itation; Spinal cord injuries; Tilt-table test. © 2010 by the AmericanCongressof Rehabilitation Medicine I N PERSONS WITH SPINAL cord injury, in addition to mot and sensory deficits, partial or complete interruption of auto- nomic cardiovascular innervation results in dysregulation of pressure. Although the etiology may vary, the prevailing tho is that blood pressure disorders in persons with tetraplegia from decentralized sympathetic neural cardiovascular contr significantly reduced plasma norepinephrine levels have been reported during HUT. 1-3 As a consequence of impaired sympa- thetic cardiovascular innervation, individuals with tetrapleg prone to chronic hypotension with exacerbations during per orthostasis. 4-8 It is well established that OH hinders the rehabil tation process during the acute and subacute phases of SCI 4,9-11 but may also hamper the resumption of independence and f tionalactivities in persons with chronic SCI. 6,10 We recently reported significantly reduced memory and marginally redu attention and processing speed and executive function in hy tensive persons with chronic SCI compared with normotens counterparts, 12 as previously reported in the non-SCI popula- tion. 13-17 Thus, chronic hypotension and OH might be expecte limitsignificantly the quality of life in persons with SCI, and treatment options should be considered. Although many persons with tetraplegia are hypotensive, they often remain clinically asymptomatic, and, for this reas treatment strategies are notroutinely considered as partof clinical care. In fact,there is a striking disparity between the available treatment options forhypertension compared with hypotension in the general population: hypertension has 119 U.S. Food and Drug Administration–approved medications, and hypotension just 1, midodrine hydrochloride. Of note, th safety and efficacy of midodrine for the treatment of chronic hypotension and OH has not been formally tested in the SCI population. The results of several case reports on the use of midodrine to treat OH in person’s with SCI suggest improve blood pressure and reduced symptoms of cerebral hypoper- From the James J. Peters Veterans Administration Medical Center, Bronx,NY, Center of Excellence (Wecht, Rosado-Rivera, Handrakis, Radulovic, Bauman), and the Medical Service (Wecht, Radulovic, Bauman), the Mount Sinai School of Med- icine, New York; Departments of Medicine (Wecht, Radulovic, Bauman) and Reha- bilitation Medicine (Wecht, Radulovic, Bauman); NYIT—School of Health Profes- sions,Old Westbury (Handrakis), NY. Presented to the Congress of Spinal Cord Medicine and Rehabilitation, September 24,2009,Dallas, TX. Supported by the Veterans AffairsRehabilitation Research and Development Service (grant nos. A6161W, B3203R, B4162C). No commercial party having a direct financial interest in the results of the research supporting this article has or will confer a benefit on the authors or on any organi- zation with which the authors are associated. Reprintrequests to Jill M. Wecht,EdD,Center of Excellence: Medical Conse- quences of Spinal Cord Injury, James J. Peters VA Medical Center, Room 1E-02, 130 West Kingsbridge Rd, Bronx,NY 10468, e-mail: JM.WECHT@VA.GOV. 0003-9993/10/9109-00307$36.00/0 doi:10.1016/j.apmr.2010.06.017 List of Abbreviations AD autonomic dysreflexia CBF cerebral blood flow HUT head-up tilt MAP mean arterial pressure MCA middle cerebral artery MFV mean blood flow velocity OH orthostatic hypotension SCI spinal cord injury TCD transcranial Doppler 1429 Arch Phys Med Rehabil Vol 91, September 2010