Efficacy of Servo-Controlled Splanchnic Venous Compression in the Treatment of Orthostatic Hypotension

Orthostatic hypotension (OH) is a significant medical problem; it occurs in ≈6% of healthy elderly in the community, 18% to 54% of nursing home residents and ≤60% in hospitalized elderly. The incidence of OH increases exponentially after the age of 65 years, and its importance is likely to increase as our population ages. OH is not only a cause of disability and impaired quality of life but it is also associated with a 2.6-fold increase in the risk of falls, and is an independent risk factor for the development of chronic kidney disease, comparable with having coronary artery disease, smoking, hypertriglyceridemia, and other risk factors that receive more attention. Moreover, OH is an independent risk factor for increased mortality. OH is particularly disabling in patients with severe impairment of autonomic pathways (neurogenic OH), who cannot engage the hemodynamic mechanisms that normally prevent the drop in blood pressure (BP) on standing. Despite its clinical importance, there are only 2 drugs approved for the treatment of neurogenic OH, the α-1 agonist midodrine and the norepinephrine prodrug droxidopa. The use of these drugs, however, is often limited by the development or worsening of supine hypertension, a common comorbidity in these patients. Abstract—Splanchnic venous pooling is a major hemodynamic determinant of orthostatic hypotension, but is not specifically targeted by pressor agents, the mainstay of treatment. We developed an automated inflatable abdominal binder that provides sustained servo-controlled venous compression (40 mm Hg) and can be activated only on standing. We tested the efficacy of this device against placebo and compared it to midodrine in 19 autonomic failure patients randomized to receive either placebo, midodrine (2.5–10 mg), or placebo combined with binder on separate days in a single-blind, crossover study. Systolic blood pressure (SBP) was measured seated and standing before and 1-hour post medication; the binder was inflated immediately before standing. Only midodrine increased seated SBP (31±5 versus 9±4 placebo and 7±5 binder, P=0.003), whereas orthostatic tolerance (defined as area under the curve of upright SBP [AUC SBP ]) improved similarly with binder and midodrine (AUC SBP , 195±35 and 197±41 versus 19±38 mm Hg×minute for placebo; P=0.003). Orthostatic symptom burden decreased with the binder (from 21.9±3.6 to 16.3±3.1, P=0.032) and midodrine (from 25.6±3.4 to 14.2±3.3, P<0.001), but not with placebo (from 19.6±3.5 to 20.1±3.3, P=0.756). We also compared the combination of midodrine and binder with midodrine alone. The combination produced a greater increase in orthostatic tolerance (AUC SBP , 326±65 versus 140±53 mm Hg×minute for midodrine alone; P=0.028, n=21) and decreased orthostatic symptoms (from 21.8±3.2 to 12.9±2.9, P<0.001). In conclusion, servo-controlled abdominal venous compression with an automated inflatable binder is as effective as midodrine, the standard of care, in the management of orthostatic hypotension. Combining both therapies produces greater improvement in orthostatic tolerance. (Hypertension. 2016;68:00-00. DOI: 10.1161/HYPERTENSIONAHA.116.07199.) • Online Data Supplement