Midodrine: Insidious development of urologic adverse effects in patients with spinal cord injury: A report of 2 cases

Abstract

Midodrine, a prodrug, is converted after oral administration into its active drug, desglymidodrine, which acts as an α₁-adrenoceptor stimulant. Midodrine is prescribed for the treatment of neurogenic orthostatic hypotension in patients with spinal cord injury. By virtue of its α₁-adrenergic effects, midodrine causes an increase in the tone of the vesical sphincter, which may silently lead to progressive retention of urine, particularly in patients with spinal cord injury who void urine spontaneously. Further, midodrine may aggravate detrusor-sphincter dyssynergia, which can lead to hydroureteronephrosis. A 68-year-old man with C-4 tetraplegia was voiding urine satisfactorily through reflex detrusor contractions. He was prescribed midodrine (5 mg at 8:00am, 5 mg at 1:00pm, and 2.5 mg at 10:00pm) for postural hypotension. During the next 7 wk, this patient experienced severe leg spasms while passing urine, and the flow of urine became very slow. Intravenous urography showed bilateral hydroureteronephrosis, although an earlier study had revealed normal kidneys. Midodrine therapy was stopped, and intermittent catheterization 4 times a day, along with oral oxybutynin, was started. After midodrine was discontinued, the leg spasms during passage of urine and slowing of the urine stream coincident with the spasms disappeared completely. The patient was able to pursue activities of daily living without taking midodrine. A 40-year-old man with C-7 tetraplegia was passing urine spontaneously with no problem. For postural hypotension, he was prescribed midodrine (5 mg in the morning and 2.5 mg at lunchtime), fludrocortisone (100 μg daily), and ephedrine (15 mg by mouth, taken 10 min before getting up in the morning). Three months later, the patient presented with sweating. During the day, he would pass only small amounts of urine, but from evening onward, he would void large volumes of urine, and the sweating would diminish. Intravenous urography showed vesical diverticula; a postmicturition film revealed moderate residual urine. This patient was able to stop taking the second dose of midodrine, but he required midodrine and ephedrine in the morning to enable him to get up without feeling dizzy. After the noon midodrine dose was stopped, the patient’s sweating diminished by late afternoon. During the morning hours, however, he continued to sweat and had difficulty passing urine. Intermittent catheterization was not possible in the community setting, and the patient remains under close follow-up. These cases illustrate that patients with cervical spinal cord injury who void spontaneously may develop insidious urologic adverse effects after taking midodrine for postural hypotension. When patients with spinal cord injury develop urologic adverse effects while taking midodrine, the drug should be stopped, and other pharmacologic agents (eg, fludrocortisone) and nonpharmacologic methods should be prescribed for management of orthostatic hypotension. If a patient continues to require midodrine to control postural hypotension, intermittent catheterization combined with antimuscarinic therapy (eg, oxybutynin) should be recommended instead of spontaneous voiding.