Treatment of orthostatic hypotension due to autonomic failure with a peripheral alpha‐adrenergic agonist (midodrine)

Abstract

The therapeutic efficacy of midodrine, an alpha-adrenergic agonist that does not cross the blood-brain barrier, was investigated in a double-blind crossover trial in seven patients with orthostatic hypotension due to autonomic failure. We identified two groups of patients: those in whom upright mean arterial pressure significantly increased (group I, n = 3) and those in whom upright mean arterial pressure decreased (group II, n = 4) during midodrine treatment. Body weight changed in a parallel manner with upright blood pressure, increasing in patients of group I and decreasing in patients of group II (p less than 0.05). Autonomic cardiovascular reflexes were significantly more impaired in patients of group II than in patients of group I. We conclude that midodrine is effective in the treatment of orthostatic hypotension only in those patients with significant preservation of autonomic reflexes. Conversely, in patients with markedly impaired baroreceptor mechanisms, treatment with midodrine may produce extracellular fluid volume depletion and exacerbate orthostatic hypotension.

The Effect of Midodrine Hydrochloride on Chronic Hypotension in Patients with Diabetes Mellitus Undergoing Hemodialysis Therapy

“…The re we re no chan ges in bi oc he mi cal and he ma to lo gic pa ra me ters af ter midod ri ne the rapy. The se sa fety re sults are con sis tent with the pre vi o us stu di es [23][24][25][26] and sug gest the sa fety of mi dod ri ne ad mi nis tra ti on in di a be tic he mo dialy sis pa ti ents.…”

“…[23][24][25] Ma jor fac tors inc lu ding tem pe ra tu re, so di um and cal ci um le vel of di aly sa te, which co uld af fect hypo ten si on we re kept cons tant in our study. The we ight of pa ti ents and amo unt of di aly tic flu id re mo val re ma i ned unc han ged; he mog lo bin and blo od bi oc he mistry, inc lu ding al bu min, cal ci um and po tas si um, we re not af fec ted du ring mi dod ri ne the rapy.…”

Modulations of autonomic cardiovascular control following acute alpha-adrenergic treatment in chronic hypotension

“…Midodrine does not cross the blood-brain barrier and, therefore, does not directly influence central nervous control of the cardiovascular system. 19,34 Hence, the autonomic modulations may be ascribed to the hemodynamic effects of the drug. As an a-receptor agonist, midodrine induces arterial and venous vasoconstriction leading to increased peripheral resistance, which, in turn, causes blood pressure elevation.…”

Symptomatic Orthostatic Hypotension/Supine Hypertension

“…28 Such evidence and concern regarding extreme levels of supine hypertension will often lead to attempted bedtime use of short-acting antihypertensive medications such as small doses of hydralazine, clonidine, or nitropaste. 19,22 Some patients will tolerate vasodilators before bedtime in combination with morning fludrocortisone; these can be titrated to balance some supine BP control with amelioration of daytime postural symptoms. Of major concern with this regimen, however, are nocturnal trips to the bathroom.…”

“…Valsalva compromises venous return. 18,25,26 High-fiber diet is recommended • Exercise may cause hypotension due to vasodilatation and can be encouraged but needs to be individually tailored 6,[25][26][27] ; hydrostatic water pressure may be beneficial in swimming and pool exercises 6,20,25 • Resting in the morning and postprandially (about 60 minutes) when postural symptomatology usually worsens 6,25,26 • Two to 2.5 L of additional fluid daily with 10 g of salt daily 3,18 • Elastic compression stockings to thigh level, custom fitted to achieve 30-40 mm Hg counterpressure, worn only during the day 1,4,6,18,20 ; consider an abdominal binder 6 • Elevate head of bed 5-10° or 6-9 inches to reduce supine hypertension and morning exacerbation of postural symptoms due to pressure diuresis 3,4,18,20,25,26 • Avoid excessive environmental temperatures (hot showers and baths) 6,25,26 • Bedtime snack or alcohol vs. supine hypertension 18,19 ; avoiding drinking water within 1 hour of bedtime and midodrine within 4 hours of bedtime, also vs. supine hypertension 4,18,22 • One or two cups of coffee, especially with meals, to reduce postprandial exacerbations 18,20 ; licorice, 3 g daily 23 • Occupational and physical therapy for ambulatory assistance to permit rapid sitting; grab aids at home; home safety evaluation …”