HDCN Article Review/Hyperlink

Flynn JJ, Mitchell MC, Caruso FS, McElligott MA

Midodrine treatment for patients with hemodialysis hypotension

Clin Nephrol (Apr) 45:261-267 1996

Hypotension during hemodialysis remains a common and vexing problem. Causes include excess ultrafiltration (or delayed refilling of the vasuclar space during ultrafiltration), increased core body temperature, abnormal release of adenosine, and possibly vasodilator cytokine production during dialysis. In addition, autonomic failure, with inhibited sympathetic outflow in response to volume depletion, plays a role in at least some patients. Sympathetic dysfunction is suggested by abnormal blood pressure response to the Valsalva maneuver, abnormal "cold pressor test", and lack of tachycardia after amyl nitrate induced (or dialysis-induced) hypotension.

This study evlauated the effects of midodrine, a prodrug that is converted to des-glymidodrine, a specific alpha-1-adrenergic agonist. This agent raises blood pressure via a constrictor effect on the arterioles and venous capacitance vessels, thus preventing venous blood pooling and enhancing venous return. The peak effect occurs about one hour after administration. 21 patients were studied. All had at least a 30 mm Hg symptomatic fall in systolic pressure during HD. Mean age was 67 yrs (range 29-89) and 13 were diabetic. Dialysis was performed using a Baxter 550 volumetric machine, with programmed decreasing ultrafiltration. Dialysate temperature was 38 degrees C. The dry weight was increased to its highest tolerable level prior to midodrine therapy. All antihypertensive medications were discontinued for 2 weeks prior to study. The lowest intra- and post-dilaysis blood pressures were monitored for 5 consecutive HD treatments as a baseline. Then midodrine 2.5 mg given pre-dialysis was begun, which was increased as necessary to 25 mg (mean dose 8 mg).

Midodrine increased the mean minimal systolic pressure from 93 to 107 mmHg (p < 0.01) and elevated mean diastolic pressure from 52 to 58 mmHg (p < 0.05). Post-dialysis blood pressures were also increased. No serious side effects were observed (one patient had scalp tingling). The authors conclude that oral midodrine appears to be a safe and effective therapy for hemodialysis hypotension.

Comment: This is a pilot study using a relatively small number of patients and is not placebo controlled. However, the results are interesting and may result in an innovative new therapy for a common problem. Of note, midodrine has been also been successfully used in clinical trials of patients with orthostatic hypotension due to autonomic insufficiency. (David J. Leehey, M.D., Loyola University at Chicago)