Effects of midodrine on exercise-induced hypotension and blood pressure recovery in autonomic failure

Abstract

We tested the hypothesis that the oral alpha1-adrenergic agonist, midodrine, would limit the fall in arterial pressure observed during exercise in patients with pure autonomic failure (PAF). Fourteen subjects with PAF underwent a stand test, incremental supine cycling exercise (25, 50, and 75 W), and ischemic calf exercise, before (control) and 1 h after ingesting 10 mg midodrine. Heart rate (ECG), beat-to-beat blood pressure (MAP, arterial catheter), cardiac output (Q, open-circuit acetylene breathing), forearm blood flow (FBF, Doppler ultrasound), and calf blood flow (CBF, venous occlusion plethysmography) were measured. The fall in MAP after standing for 2 min was similar ( approximately 60 mmHg; P = 0.62). Supine MAP immediately before cycling was greater after midodrine (124 +/- 6 vs 117 +/- 6 mmHg; P < 0.03), but cycling caused a workload-dependent hypotension (P < 0.001), whereas increases in Q were modest but similar. Midodrine increased MAP and total peripheral resistance (TPR) during exercise (P < 0.04), but the exercise-induced fall in MAP and TPR were similar during control and midodrine (P = 0.27 and 0.14). FBF during cycling was not significantly reduced by midodrine (P > 0.2). By contrast, recovery of MAP after cycling was faster (P < 0.04) after midodrine ( approximately 25 mmHg higher after 5 min). Ischemic calf exercise evoked similar peak CBF in both trials, but midodrine reduced the hyperemic response over 5 min of recovery (P < 0.02). We conclude midodrine improves blood pressure and TPR during exercise and dramatically improves the recovery of MAP after exercise.

Hemodynamic determinants of chronic hypotension and their modification through vasopressor application

“…In study I, sympathomimetic treatment led to a rise in both systolic and diastolic blood pressure into the normotensive range. This is in line with previously reported blood pressure enhancement through this substance in healthy volunteers and patients with neurogenic orthostatic hypotension [16,22,23]. As a selective alpha-receptor agonist, midodrine induces arterial and venous vasoconstriction, leading to increased peripheral resistance and arterial pressure [21].…”

“…The alpha-adrenergic agonist midodrine, which was applied in the present study, is highly effective in inducing arterial and venous vasoconstriction [21]. The substance has been shown to significantly increase blood pressure in healthy subjects, as well as patients with neurogenic orthostatic hypotension [14,16,22,23].…”

Effects of water drinking on cardiovascular responses to supine exercise and on orthostatic hypotension after exercise in pure autonomic failure

“…In AF, hypotension caused by exercise, and also post-exercise OH, is difficult to treat effectively, in contrast with OH worsened by food ingestion. There is only limited benefit from medications such as midodrine and octreotide 19 20. There were subjective and objective benefits of water drinking on OH post-exercise in our patients with PAF, and ingestion of water pre-exertion is suggested.…”

Midodrine Efficacy in Orthostatic Hypotension

“…The studies by Schrage and Axelrod are described as being performed "in 23 patients who received placebo and midodrine separated by a wash out period"-neither of these studies used placebo or a wash out period, both were simple pre/post-dose assessments. 6,7 …”

“…The studies by Schrage and Axelrod are described as being performed "in 23 patients who received placebo and midodrine separated by a wash out period"-neither of these studies used placebo or a wash out period, both were simple pre/post-dose assessments. 6,7 Among the nine studies included in the meta-analysis, between two and four studies were included for pooling the different endpoints, although data would have been available from more of these studies for each endpoint. As outlined above, pooling data from these highly inhomogeneous studies is a mistake regardless, yet it is entirely unclear why some studies were chosen for pooling data for one endpoint, and others for another endpoint, although the information was similarly available for both.…”