Effects of 30-Day Midodrine Administration, Compared to Placebo, on Blood Pressure, Cerebral Blood Flow Velocity, and Cognitive Performance in Persons with SCI

Abstract

Background: Individuals with spinal cord injury (SCI) at and above T6 experience impaired descending cortical control of the autonomic nervous system, which predisposes them to blood pressure (BP) disorders including persistent hypotension.

Objectives: The primary aim of this investigation was to determine the effects of midodrine, 10 mg, administered daily over a 30-day period in the home environment, compared to placebo, on laboratory assessments of BP, cerebral blood flow velocity (CBFv), and cognitive performance in hypotensive individuals with chronic SCI.

Methods: This prospective, randomized, placebo-controlled, double-blind, crossover trial was conducted in 15 individuals with tetraplegia. In the first 30-day period, five participants were randomized to midodrine and 10 were randomized to placebo; participants were then crossed over to the second 30-day period following a 14-day washout. Laboratory assessments of BP, CBFv, and cognitive performance were measured before and after each of the two study arms.

Results: Systolic BP (SBP) was significantly increased following midodrine administration compared to placebo (116 ± 23 mm Hg vs 94 ± 16 mm Hg; p = .002). In addition, diastolic CBFv was increased after midodrine administration compared to placebo (31.0 ± 11.2 vs 25.6 ± 9.1 cm/s; p = .04). However, there were no significant drug by time interaction effects for systolic or mean CBFv (p > .172) and cognitive performance (p = .689).

Conclusion: The results suggest significant increases in SBP and diastolic CBFv without appreciable effects on cognition after 30 days of midodrine administration. Further investigation is needed to identify effective antihypotensive treatment options that not only normalize BP but also improve CBFv and cognition.

Keywords: autonomic dysreflexia; hemodynamic instability; hypotension; orthostatic hypotension; spinal cord injuries; tetraplegia.

Figure 1.

Hemodynamic and cerebrovascular responses during Hopkins Verbal Learning Test-Revised (HVLT) before and after 30 days of drug administration. There were no significant differences in heart rate (HR; placebo: 72 ± 22 bpm vs midodrine: 65 ± 13 bpm), systolic blood pressure (SBP; placebo: 96 ± 16 mm Hg vs midodrine: 120 ± 27 mm Hg), and diastolic flow velocity (dFV; placebo: 25 ± 8 cm/s vs midodrine: 30 ± 13 cm/s) when analyzing by test (placebo: 43.6 ± 18.3 vs midodrine: 37.8 ± 13.8) after taking midodrine for 30 days compared to placebo. The red line represents the average hemodynamic and cerebrovascular response during HVLT.

Figure 2.

Hemodynamic and cerebrovascular responses during Symbol Digit Modalities Test (SDMT) before and after 30 days of drug administration. There were no significant differences in heart rate (HR; placebo: 72 ± 20 bpm vs midodrine: 65 ± 6 bpm), systolic blood pressure (SBP; placebo: 99 ± 17 mm Hg vs midodrine: 121 ± 17 mm Hg), and diastolic flow velocity (dFV; placebo: 27 ± 10 cm/s vs midodrine: 31 ± 12 cm/s) when analyzing by test (placebo: 49.0 ± 8.5 vs midodrine: 45.9 ± 6.9) after taking midodrine for 30 days compared to placebo. The red line represents the average hemodynamic and cerebrovascular response during SDMT.

Figure 3.

Hemodynamic and cerebrovascular responses during verbal fluency before and after 30 days of drug administration. There were no significant differences in heart rate (HR; placebo: 71 ± 20 bpm vs midodrine: 65 ± 10 bpm), systolic blood pressure (SBP; placebo: 99 ± 17 mm Hg vs midodrine: 126 ± 25 mm Hg), and diastolic flow velocity (dFV; placebo: 29 ± 10 cm/s vs midodrine: 30 ± 11 cm/s) when analyzing by test (placebo: 25.6 ± 4.8 vs midodrine: 24.8 ± 4.2) after taking midodrine for 30 days compared to placebo. The red line represents the average hemodynamic and cerebrovascular response during verbal fluency.