HDCN Article Review/Hyperlink

Blowey DL, Balfe JW, Gupta I, Gajaria MM, Koren G

Midodrine efficacy and pharmacokinetics in a patient with recurrent intradialytic hypotension

Am J Kidney Dis (Jul) 28:132-136 1996

How to treat dialysis patients with refractory hypotension is an important clinical problem. Given recent data that expected increases in plasma vasopressin or norepinephrine levels fail to occur, and that there is paradoxic withdrawal of peroneal nerve sympathetic tone during or just prior to hypotensive episodes, predialysis administration of phenylephrine, amezinium, or vasopressin has been tried. Midodrine is an alpha-agonist prodrug with high oral bioavailability which is metabolized to its active component, de-glymidodrine, the latter having a plasma half-life of about 3 hours in patients with normal renal function (but which is prolonged in ESRD). Midodrine has been used successfully to treat to treat idiopathic orthostatic hypotension and hypotension in Shy Drager syndrome.

In his paper, Blowey et al had an 18 year old patient with ESRD and who also had Bardet-Biedl syndrome (polydactyly, obesity, tapetoretinal degeneration, mental retardation, hypogonadism, and renal involvement) who had precipitous, symptomatic falls in BP during dialysis, which persisted even after use of ramped sodium dialysis and use of cool dialysate. A tilt table test showed marked hypotension within 20 min of tilting, even when 2 kg over dry weight. The intradialytic hypotension was improved markedly with 5 mg administration of midodrine predialysis, and completely resolved when the dose was increased to 10 mg. After 4 months, the midodrine was tapered and then discontinued, without recurrence of the hypotension. Pharmacokinetic studies also were done. Plasma half-life was 10 hours off dialysis and 1.4 hours during dialysis. Continuous ambulatory BP monitoring showed that the mean interdialytic BP was significantly increased. This, and the long plasma half-life in this patient off dialysis probably warrant some caution in chronic use of this agent.

Comment: Recurrent hypotensive episodes during dialysis have been associated with poor outcome. However, it is not clear if chronic midodrine administration to such patients would increase their survival or decrease morbidity. The encouraging results in this paper are preliminary, but suggest that further trials of midodrine are warranted in hypotension-prone dialysis patients. It is unclear to me why the patient unltimately improved and eventually no longer required midodrine. (John T. Daugirdas, M.D., University of Illinois at Chicago)